{"id":23274,"date":"2021-10-19T11:01:07","date_gmt":"2021-10-19T11:01:07","guid":{"rendered":"https:\/\/evaggelatos.com\/?p=23274"},"modified":"2021-10-20T05:47:10","modified_gmt":"2021-10-20T05:47:10","slug":"%cf%84%ce%b5%cf%87%ce%bd%ce%b9%ce%ba%ce%ac-%ce%ba%ce%b1%cf%84%ce%b1%cf%83%ce%ba%ce%b5%cf%85%ce%b1%cf%83%ce%bc%ce%ad%ce%bd%ce%bf%cf%82-%ce%b9%cf%8c%cf%82-%cf%80%ce%bf%cf%85-%ce%b4%cf%8c%ce%b8%ce%b7","status":"publish","type":"post","link":"https:\/\/evaggelatos.com\/?p=23274","title":{"rendered":"\u03a4\u03b5\u03c7\u03bd\u03b9\u03ba\u03ac \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03b1\u03c3\u03bc\u03ad\u03bd\u03bf\u03c2 \u03bf \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03cc\u03c2 \u03c0\u03bf\u03c5 \u03bc\u03b5\u03c4\u03b1\u03c6\u03ad\u03c1\u03b8\u03b7\u03ba\u03b5 \u03bc\u03b5 3,7\u03b5\u03ba\u03b1\u03c4\u03bf\u03bc\u03bc\u03cd\u03c1\u03b9\u03b1 $ \u03b5\u03bd\u03af\u03c3\u03c7\u03c5\u03c3\u03b7 \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u0397\u03a0\u0391 \u03c3\u03c4\u03b7 WUHAN \u03bd\u03b1 \u03c4\u03bf\u03bd \u03b1\u03bd\u03b1\u03c0\u03c4\u03cd\u03be\u03b5\u03b9 \u03ba\u03b1\u03b9 \u03b5\u03be\u03b1\u03c0\u03bf\u03bb\u03cd\u03c3\u03b5\u03b9 \u03b1\u03c0\u03cc \u03c4\u03bf\u03bd Antony Fauci, Ralf Baric \u03ba\u03b1\u03b9 \u03a3\u03b9\u03b1."},"content":{"rendered":"<div class=\"c-context-bar c-context-bar--sticky\" data-component=\"context-bar\" aria-hidden=\"true\">\n<div class=\"c-context-bar__container u-container\"><strong>\u03a4\u03bf \u03c0\u03b1\u03c1\u03b1\u03ba\u03ac\u03c4\u03c9 \u03ac\u03c1\u03b8\u03c1\u03bf \u03ad\u03ba\u03b1\u03bd\u03b5 \u03b5\u03bd\u03c4\u03cd\u03c0\u03c9\u03c3\u03b7 \u03bf\u03bb\u03bf\u03c3\u03c7\u03b5\u03c1\u03ce\u03c2 \u03b1\u03c1\u03bd\u03b7\u03c4\u03b9\u03ba\u03ae \u03c3\u03c4\u03b7\u03bd \u03b9\u03b1\u03c4\u03c1\u03cc , \u03b5\u03c1\u03b5\u03c5\u03bd\u03ae\u03c4\u03b9\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c5\u03b3\u03b3\u03c1\u03b1\u03c6\u03ad\u03b1 Meryl Nass \u03b7 \u03bf\u03c0\u03bf\u03af\u03b1 \u03c4\u03bf \u03b2\u03c1\u03ae\u03ba\u03b5 \u03cc\u03c7\u03b9 \u03b1\u03c0\u03bb\u03ce\u03c2 \u03b1\u03c4\u03b5\u03bb\u03ad\u03c2 \u03b1\u03bb\u03bb\u03ac \u03cc\u03c4\u03b9 \u03ba\u03ac\u03c4\u03b9 \u03b4\u03b5\u03bd \u03c0\u03ae\u03b3\u03b1\u03b9\u03bd\u03b5 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03c1\u03c9\u03c4\u03ae\u03b8\u03b7\u03ba\u03b5 \u03c0\u03c9\u03c2 \u03c4\u03cc\u03c3\u03bf\u03c5 \u03b5\u03c5\u03b7\u03c0\u03cc\u03bb\u03b7\u03c0\u03c4\u03bf\u03b9 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03c4\u03b1\u03be\u03b9\u03c9\u03bc\u03ad\u03bd\u03bf\u03b9 \u03c3\u03c5\u03bd\u03ac\u03b4\u03b5\u03bb\u03c6\u03bf\u03b9 \u03ae\u03c4\u03b1\u03bd \u03b4\u03c5\u03bd\u03b1\u03c4\u03cc\u03bd \u03bd\u03b1 \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03bf\u03c5\u03bd \u03b1\u03c5\u03c4\u03cc \u03c4\u03bf \u03ac\u03c1\u03b8\u03c1\u03bf \u03b3\u03b9\u03b1 \u03bd\u03b1 \u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03ae\u03c3\u03bf\u03c5\u03bd \u03ba\u03b1\u03b9 \u03bd\u03b1 \u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03bf\u03cd\u03bd \u03bc\u03ad\u03c7\u03c1\u03b9 \u03c3\u03ae\u03bc\u03b5\u03c1\u03b1 \u03ba\u03ac\u03c4\u03b9 \u03c0\u03bf\u03c5 \u03ae\u03c4\u03b1\u03bd \u03b5\u03be \u03b1\u03c1\u03c7\u03ae\u03c2 \u03ba\u03b1\u03c4\u03b1\u03c6\u03b1\u03bd\u03ad\u03c2 \u03b3\u03b9&#8217; \u03b1\u03c5\u03c4\u03ae\u03bd&#8230;<\/strong><\/div>\n<div><\/div>\n<div><strong>\u03a0\u03c9\u03c2 \u03bf \u03b9\u03cc\u03c2 \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03ac\u03c3\u03c4\u03b7\u03ba\u03b5 \u03c0\u03b5\u03b9\u03c1\u03b1\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03c3\u03b5 \u03b5\u03c1\u03b3\u03b1\u03c3\u03c4\u03ae\u03c1\u03b9\u03bf \u03bc\u03b5 \u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03bf\u03c5\u03c2 \u03c3\u03c4\u03cc\u03c7\u03bf\u03c5\u03c2. <\/strong><\/div>\n<div><\/div>\n<div><strong>\u039a\u03b1\u03b9 \u03c3\u03b1\u03bd \u03b5\u03c0\u03b9\u03c3\u03c4\u03ad\u03b3\u03b1\u03c3\u03bc\u03b1 \u03b1\u03ba\u03bf\u03bb\u03bf\u03cd\u03b8\u03b7\u03c3\u03b5 \u03bf \u039d\u03bf\u03bc\u03c0\u03b5\u03bb\u03af\u03c3\u03c4\u03b1\u03c2 Luk Montagnier \u03bf \u03bf\u03c0\u03bf\u03af\u03bf\u03c2 \u03b5\u03af\u03c0\u03b5:<span style=\"font-size: 18pt;\"> \u00a8\u0395\u03b3\u03ce \u03bc\u03b9\u03bb\u03ce \u03bc\u03b5 \u03ba\u03b1\u03b8\u03b1\u03c1\u03ac \u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03bf\u03bd\u03b9\u03ba\u03ac \u03b4\u03b5\u03b4\u03bf\u03bc\u03ad\u03bd\u03b1 \u03ba\u03b1\u03b9 \u03cc\u03c7\u03b9 \u03c5\u03c0\u03bf\u03b8\u03ad\u03c3\u03b5\u03b9\u03c2. \u0397 \u03b1\u03bb\u03bb\u03b7\u03bb\u03bf\u03c5\u03c7\u03af\u03b1 \u03c4\u03bf\u03c5 \u03b3\u03bf\u03bd\u03b9\u03b4\u03b9\u03ce\u03bc\u03b1\u03c4\u03bf\u03c2 \u03c4\u03bf\u03c5 Sars-COV-2 \u03b4\u03b5\u03af\u03c7\u03bd\u03b5\u03b9 \u03b1\u03bd\u03b8\u03c1\u03ce\u03c0\u03b9\u03bd\u03b7 \u03b5\u03c0\u03ad\u03bc\u03b2\u03b1\u03c3\u03b7. \u03a0\u03c1\u03cc\u03ba\u03b5\u03b9\u03c4\u03b1\u03b9 \u03b3\u03b9\u03b1 \u03c4\u03b5\u03c7\u03bd\u03b9\u03ba\u03ac \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03b1\u03c3\u03bc\u03ad\u03bd\u03bf \u03b9\u03cc&#8221;.<\/span> \u0394\u03b5\u03af\u03c4\u03b5 \u03c4\u03bf \u03c0\u03b1\u03c1\u03b1\u03ba\u03ac\u03c4\u03c9 \u03b2\u03af\u03bd\u03c4\u03b5\u03bf \u03b1\u03c0\u03bf\u03ba\u03b1\u03bb\u03bf\u03cd\u03bc\u03b5\u03bd\u03bf &#8220;\u03a0\u0391\u039d\u0394\u0397\u039c\u0399\u0391&#8221; \u03ba\u03b1\u03b9 \u03b1\u03c6\u03bf\u03cd \u03b4\u03b9\u03b1\u03b2\u03ac\u03c3\u03b5\u03c4\u03b5 \u03c4\u03bf \u03c0\u03b9\u03bf \u03ba\u03ac\u03c4\u03c9 \u03b4\u03ae\u03b8\u03b5\u03bd \u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03bf\u03bd\u03b9\u03ba\u03cc \u03ac\u03c1\u03b8\u03c1\u03bf-\u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03af\u03b1, \u03b2\u03b3\u03ac\u03bb\u03c4\u03b5 \u03bc\u03cc\u03bd\u03bf\u03b9 \u03c3\u03b1\u03c2 \u03c4\u03bf \u03c3\u03c5\u03bc\u03c0\u03ad\u03c1\u03b1\u03c3\u03bc\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03c0\u03b1\u03b3\u03ba\u03cc\u03c3\u03bc\u03b9\u03b1 \u03b1\u03c0\u03ac\u03c4\u03b7 \u03c0\u03bf\u03c5 \u03bb\u03ad\u03b3\u03b5\u03c4\u03b1\u03b9 <span style=\"font-size: 18pt;\">\u03c0\u03b1\u03bd\u03b4\u03b7\u03bc\u03af\u03b1 \u03b5\u03ba \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd.<\/span><\/strong><\/div>\n<\/div>\n<article lang=\"en\">\n<div class=\"c-article-header\">\n<header><a href=\"http:\/\/https:\/\/www.youtube.com\/watch?time_continue=934&#038;v=PSQw3hWPfWg&#038;feature=emb_logo\">http:\/\/https:\/\/www.youtube.com\/watch?time_continue=934&amp;v=PSQw3hWPfWg&amp;feature=emb_logo<\/a><\/p>\n<h1 class=\"c-article-title\" data-test=\"article-title\" data-article-title=\"\">\u03a4\u03bf \u03c0\u03bf\u03bb\u03cd \u03b3\u03bd\u03c9\u03c3\u03c4\u03cc \u03c0\u03b5\u03c1\u03b9\u03bf\u03b4\u03b9\u03ba\u03cc Nature Medicine \u03b4\u03b9\u03b1\u03c6\u03c9\u03bd\u03b5\u03af, \u03bf \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03cc\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03b1\u03c0\u03bf\u03c4\u03ad\u03bb\u03b5\u03c3\u03bc\u03b1 \u03bc\u03b5\u03c4\u03b1\u03bb\u03bb\u03ac\u03be\u03b5\u03c9\u03bd \u03b1\u03c0\u03cc \u03b6\u03ce\u03bf (\u03bd\u03c5\u03c7\u03c4\u03b5\u03c1\u03af\u03b4\u03b1) \u03ba\u03b1\u03b9 \u03bc\u03cc\u03bb\u03c5\u03bd\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03b1\u03bd\u03b8\u03c1\u03ce\u03c0\u03bf\u03c5 \u03c0\u03b1\u03c1\u03ac \u03c4\u03b5\u03c7\u03bd\u03b7\u03c4\u03ae\u03c2 \u03c4\u03c1\u03bf\u03c0\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2.<\/h1>\n<h1 class=\"c-article-title\" data-test=\"article-title\" data-article-title=\"\">The proximal origin of SARS-CoV-2<\/h1>\n<ul>\n<li><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#article-info\" data-track=\"click\" data-track-action=\"publication date\" data-track-label=\"link\">Published: <time datetime=\"2020-03-17\">17 March 2020<\/time><\/a><\/li>\n<\/ul>\n<ul class=\"c-article-author-list js-etal-collapsed js-no-scroll\" data-etal=\"25\" data-etal-small=\"3\" data-test=\"authors-list\" data-component-authors-activator=\"authors-list\">\n<li class=\"c-article-author-list__item\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#auth-Kristian_G_-Andersen\" data-test=\"author-name\" data-track=\"click\" data-track-action=\"open author\" data-track-label=\"link\" data-author-popup=\"auth-Kristian_G_-Andersen\" data-corresp-id=\"c1\"><span style=\"font-size: 14pt;\">Kristian G. Andersen<\/span><\/a><span style=\"font-size: 14pt;\">,<\/span><\/li>\n<li class=\"c-article-author-list__item\"><span style=\"font-size: 14pt;\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#auth-Andrew-Rambaut\" data-test=\"author-name\" data-track=\"click\" data-track-action=\"open author\" data-track-label=\"link\" data-author-popup=\"auth-Andrew-Rambaut\">Andrew Rambaut<\/a>,<\/span><\/li>\n<li class=\"c-article-author-list__item js-smaller-author-etal\"><span style=\"font-size: 14pt;\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#auth-W__Ian-Lipkin\" data-test=\"author-name\" data-track=\"click\" data-track-action=\"open author\" data-track-label=\"link\" data-author-popup=\"auth-W__Ian-Lipkin\">W. Ian Lipkin<\/a>,<\/span><\/li>\n<li class=\"c-article-author-list__item js-smaller-author-etal\"><span style=\"font-size: 14pt;\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#auth-Edward_C_-Holmes\" data-test=\"author-name\" data-track=\"click\" data-track-action=\"open author\" data-track-label=\"link\" data-author-popup=\"auth-Edward_C_-Holmes\">Edward C. Holmes<\/a> &amp;<\/span><\/li>\n<li class=\"c-article-author-list__item\"><span style=\"font-size: 14pt;\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#auth-Robert_F_-Garry\" data-test=\"author-name\" data-track=\"click\" data-track-action=\"open author\" data-track-label=\"link\" data-author-popup=\"auth-Robert_F_-Garry\">Robert F. Garry<\/a>\u00a0<\/span><\/li>\n<\/ul>\n<p class=\"c-article-info-details\" data-container-section=\"info\"><a href=\"https:\/\/www.nature.com\/nm\" data-test=\"journal-link\"><i data-test=\"journal-title\">Nature Medicine<\/i><\/a> <b data-test=\"journal-volume\"><span class=\"u-visually-hidden\">volume<\/span>\u00a026<\/b>,\u00a0<span class=\"u-visually-hidden\">pages <\/span>450\u2013452 (<span data-test=\"article-publication-year\">2020<\/span>)<a class=\"c-article-info-details__cite-as u-hide-print\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#citeas\" data-track=\"click\" data-track-action=\"cite this article\" data-track-label=\"link\">Cite this article<\/a><\/p>\n<div class=\"c-article-metrics-bar__wrapper u-clear-both\">\n<ul class=\"c-article-metrics-bar u-list-reset\">\n<li class=\"c-article-metrics-bar__item\">\n<p class=\"c-article-metrics-bar__details\"><a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9\/metrics\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"view metrics\" data-track-label=\"link\">Metrics <span class=\"u-visually-hidden\">details<\/span><\/a><\/p>\n<\/li>\n<\/ul>\n<\/div>\n<\/header>\n<\/div>\n<div class=\"c-article-body\">\n<div class=\"c-article-section__content\">\n<p><span style=\"font-size: 14pt;\"><b>To the Editor<\/b> \u2014 Since the first reports of novel pneumonia (COVID-19) in Wuhan, Hubei province, China<sup><a id=\"ref-link-section-d6507832e435\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e438\" title=\"Wu, F. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>, there has been considerable discussion on the origin of the causative virus, SARS-CoV-2<sup><a id=\"ref-link-section-d6507832e442\" title=\"Gorbalenya, A. E. et al. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.07.937862 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR3\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 3\">3<\/a><\/sup> (also referred to as HCoV-19)<sup><a id=\"ref-link-section-d6507832e446\" title=\"Jiang, S. et al. Lancet https:\/\/doi.org\/10.1016\/S0140-6736(20)30419-0 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR4\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\">4<\/a><\/sup>. Infections with SARS-CoV-2 are now widespread, and as of 11 March 2020, 121,564 cases have been confirmed in more than 110 countries, with 4,373 deaths<sup><a id=\"ref-link-section-d6507832e450\" title=\"Dong, E., Du, H. &amp; Gardner, L. Lancet Infect. Dis. https:\/\/doi.org\/10.1016\/S1473-3099(20)30120-1 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR5\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\">5<\/a><\/sup>.<\/span><\/p>\n<\/div>\n<div class=\"c-article-section__content\">\n<p><span style=\"font-size: 14pt;\">SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms<sup><a id=\"ref-link-section-d6507832e457\" title=\"Corman, V. M., Muth, D., Niemeyer, D. &amp; Drosten, C. Adv. Virus Res. 100, 163\u2013188 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR6\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 6\">6<\/a><\/sup>. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.<\/span><\/p>\n<\/div>\n<section data-title=\"Notable features of the SARS-CoV-2 genome\">\n<div id=\"Sec1-section\" class=\"c-article-section\">\n<h2 id=\"Sec1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Notable features of the SARS-CoV-2 genome<\/h2>\n<div id=\"Sec1-content\" class=\"c-article-section__content\">\n<p><span style=\"font-size: 14pt;\">Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies<sup><a id=\"ref-link-section-d6507832e468\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">7<\/a>,<a id=\"ref-link-section-d6507832e468_1\" title=\"Walls, A. C. et al. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.956581 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">8<\/a>,<a id=\"ref-link-section-d6507832e471\" title=\"Wrapp, D. et al. Science https:\/\/doi.org\/10.1126\/science.abb2507 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR9\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\">9<\/a><\/sup> and biochemical experiments<sup><a id=\"ref-link-section-d6507832e475\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e478\" title=\"Wrapp, D. et al. Science https:\/\/doi.org\/10.1126\/science.abb2507 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR9\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\">9<\/a>,<a id=\"ref-link-section-d6507832e481\" title=\"Letko, M., Marzi, A. &amp; Munster, V. Nat. Microbiol. https:\/\/doi.org\/10.1038\/s41564-020-0688-y (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR10\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\">10<\/a><\/sup>, SARS-CoV-2 appears to be optimized for <strong>binding to the human receptor ACE2;<\/strong> and (ii) the spike protein of SARS-CoV-2 has <strong>a functional polybasic (furin) cleavage site at the S1\u2013S2 boundary through the insertion of 12 nucleotides<sup><a id=\"ref-link-section-d6507832e485\" title=\"Walls, A. C. et al. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.956581 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\">8<\/a><\/sup>, which additionally led to the predicted acquisition of three O-linked glycans around the site.<\/strong><\/span><\/p>\n<h3 id=\"Sec2\" class=\"c-article__sub-heading\">1. Mutations in the receptor-binding domain of SARS-CoV-2<\/h3>\n<p><span style=\"font-size: 14pt;\">The receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome<sup><a id=\"ref-link-section-d6507832e496\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e499\" title=\"Wu, F. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors and for determining the host range of SARS-CoV-like viruses<sup><a id=\"ref-link-section-d6507832e503\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup>. With coordinates based on SARS-CoV, they are Y442, L472, N479, D480, T487 and Y4911, which correspond to L455, F486, Q493, S494, N501 and Y505 in SARS-CoV-2<sup><a id=\"ref-link-section-d6507832e507\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup>. Five of these six residues differ between SARS-CoV-2 and SARS-CoV (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1a<\/a>). On the basis of structural studies<sup><a id=\"ref-link-section-d6507832e514\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">7<\/a>,<a id=\"ref-link-section-d6507832e514_1\" title=\"Walls, A. C. et al. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.956581 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\">8<\/a>,<a id=\"ref-link-section-d6507832e517\" title=\"Wrapp, D. et al. Science https:\/\/doi.org\/10.1126\/science.abb2507 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR9\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\">9<\/a><\/sup> and biochemical experiments<sup><a id=\"ref-link-section-d6507832e522\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e525\" title=\"Wrapp, D. et al. Science https:\/\/doi.org\/10.1126\/science.abb2507 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR9\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\">9<\/a>,<a id=\"ref-link-section-d6507832e528\" title=\"Letko, M., Marzi, A. &amp; Munster, V. Nat. Microbiol. https:\/\/doi.org\/10.1038\/s41564-020-0688-y (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR10\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\">10<\/a><\/sup>, <strong>SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans, ferrets, (\u03bd\u03c5\u03c6\u03af\u03c4\u03c3\u03b5\u03c2), cats and other species with high receptor homology<sup><a id=\"ref-link-section-d6507832e532\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup>.<\/strong><\/span><\/p>\n<div id=\"figure-1\" class=\"c-article-section__figure js-c-reading-companion-figures-item\" data-test=\"figure\" data-container-section=\"figure\" data-title=\"Features of the spike protein in human SARS-CoV-2 and related coronaviruses.\">\n<figure><figcaption><b id=\"Fig1\" class=\"c-article-section__figure-caption\" data-test=\"figure-caption-text\">Fig. 1: Features of the spike protein in human SARS-CoV-2 and related coronaviruses.<\/b><\/figcaption><div class=\"c-article-section__figure-content\">\n<div class=\"c-article-section__figure-item\"><a class=\"c-article-section__figure-link\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9\/figures\/1\" rel=\"nofollow\" data-test=\"img-link\" data-track=\"click\" data-track-label=\"image\" data-track-action=\"view figure\"><picture><source srcset=\"\/\/media.springernature.com\/lw685\/springer-static\/image\/art%3A10.1038%2Fs41591-020-0820-9\/MediaObjects\/41591_2020_820_Fig1_HTML.png?as=webp\" type=\"image\/webp\" \/><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/media.springernature.com\/lw685\/springer-static\/image\/art%3A10.1038%2Fs41591-020-0820-9\/MediaObjects\/41591_2020_820_Fig1_HTML.png\" alt=\"figure1\" width=\"793\" height=\"375\" aria-describedby=\"Fig1\" \/><\/picture><\/a><\/div>\n<div id=\"figure-1-desc\" class=\"c-article-section__figure-description\" data-test=\"bottom-caption\">\n<p><span style=\"font-size: 14pt;\"><b>a<\/b>, Mutations in contact residues of the SARS-CoV-2 spike protein. The spike protein of SARS-CoV-2 (red bar at top) was aligned against the most closely related SARS-CoV-like coronaviruses and SARS-CoV itself. Key residues in the spike protein that make contact to the ACE2 receptor are marked with blue boxes in both SARS-CoV-2 and related viruses, including SARS-CoV (Urbani strain). <b>b<\/b>, Acquisition of polybasic cleavage site and O-linked glycans. Both the polybasic cleavage site and the three adjacent predicted O-linked glycans are unique to SARS-CoV-2 and were not previously seen in lineage B betacoronaviruses. Sequences shown are from NCBI GenBank, accession codes <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/MN908947\">MN908947<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/MN996532\">MN996532<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/AY278741\">AY278741<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/KY417146\">KY417146<\/a> and <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/MK211376\">MK211376<\/a>. The pangolin coronavirus sequences are a consensus generated from <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/sra\/SRR10168377\/\">SRR10168377<\/a> and <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/sra\/?term=SRR10168378\">SRR10168378<\/a> (NCBI BioProject <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/?term=PRJNA573298\">PRJNA573298<\/a>)<sup><a id=\"ref-link-section-d6507832e581\" title=\"Wong, M. C., Javornik Cregeen, S. J., Ajami, N. J. &amp; Petrosino, J. F. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.07.939207 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR29\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 29\">29<\/a>,<a id=\"ref-link-section-d6507832e584\" title=\"Liu, P., Chen, W. &amp; Chen, J.-P. Viruses 11, 979 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR30\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 30\">30<\/a><\/sup>.<\/span><\/p>\n<\/div>\n<\/div>\n<div class=\"u-text-right u-hide-print\"><a class=\"c-article__pill-button\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9\/figures\/1\" rel=\"nofollow\" data-test=\"article-link\" data-track=\"click\" data-track-label=\"button\" data-track-action=\"view figure\" data-track-dest=\"link:Figure1 Full size image\" aria-label=\"Full size image figure 1\"><span style=\"font-size: 18pt;\">Full size image<\/span><\/a><\/div>\n<\/figure>\n<\/div>\n<p><span style=\"font-size: 18pt;\">While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal<sup><a id=\"ref-link-section-d6507832e593\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup> and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding<sup><a id=\"ref-link-section-d6507832e597\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a>,<a id=\"ref-link-section-d6507832e600\" title=\"Sheahan, T. et al. J. Virol. 82, 2274\u20132285 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR11\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\">11<\/a><\/sup>. <strong>Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.<\/strong><\/span><\/p>\n<h3 id=\"Sec3\" class=\"c-article__sub-heading\">2. Polybasic furin cleavage site and O-linked glycans<\/h3>\n<p><span style=\"font-size: 14pt;\">The second notable feature of SARS-CoV-2 is a polybasic cleavage site (RRAR) at the junction of S1 and S2, the two subunits of the spike<sup><a id=\"ref-link-section-d6507832e612\" title=\"Walls, A. C. et al. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.956581 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR8\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\">8<\/a><\/sup> (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1b<\/a>). This allows effective cleavage by furin and other proteases and has a role in determining viral infectivity and host range<sup><a id=\"ref-link-section-d6507832e619\" title=\"Nao, N. et al. MBio 8, e02298-16 (2017).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR12\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 12\">12<\/a><\/sup>. In addition, a leading proline is also inserted at this site in SARS-CoV-2; thus, the inserted sequence is PRRA (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1b<\/a>). The turn created by the proline is predicted to result in the addition of O-linked glycans to S673, T678 and S686, which flank the cleavage site and are unique to SARS-CoV-2 (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1b<\/a>). Polybasic cleavage sites have not been observed in related \u2018lineage B\u2019 betacoronaviruses, although other human betacoronaviruses, including HKU1 (lineage A), have those sites and predicted O-linked glycans<sup><a id=\"ref-link-section-d6507832e630\" title=\"Chan, C.-M. et al. Exp. Biol. Med. 233, 1527\u20131536 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR13\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 13\">13<\/a><\/sup>. Given the level of genetic variation in the spike, it is likely that SARS-CoV-2-like viruses with partial or full polybasic cleavage sites will be discovered in other species.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The functional consequence of the polybasic cleavage site in SARS-CoV-2 is unknown, and it will be important to determine its impact on transmissibility and pathogenesis in animal models. Experiments with SARS-CoV have shown that insertion of a furin cleavage site at the S1\u2013S2 junction enhances cell\u2013cell fusion without affecting viral entry<sup><a id=\"ref-link-section-d6507832e637\" title=\"Follis, K. E., York, J. &amp; Nunberg, J. H. Virology 350, 358\u2013369 (2006).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR14\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 14\">14<\/a><\/sup>. In addition, efficient cleavage of the MERS-CoV spike enables MERS-like coronaviruses from bats to infect human cells<sup><a id=\"ref-link-section-d6507832e641\" title=\"Menachery, V. D. et al. J. Virol. https:\/\/doi.org\/10.1128\/JVI.01774-19 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR15\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 15\">15<\/a><\/sup>. In avian influenza viruses, rapid replication and transmission in highly dense chicken populations selects for the acquisition of polybasic cleavage sites in the hemagglutinin (HA) protein<sup><a id=\"ref-link-section-d6507832e645\" title=\"Alexander, D. J. &amp; Brown, I. H. Rev. Sci. Tech. 28, 19\u201338 (2009).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR16\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 16\">16<\/a><\/sup>, which serves a function similar to that of the coronavirus spike protein. <strong>Acquisition of polybasic cleavage sites in HA, by insertion or recombination, converts low-pathogenicity avian influenza viruses into highly pathogenic forms<sup><a id=\"ref-link-section-d6507832e649\" title=\"Alexander, D. J. &amp; Brown, I. H. Rev. Sci. Tech. 28, 19\u201338 (2009).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR16\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 16\">16<\/a><\/sup>. The acquisition of polybasic cleavage sites by HA has also been observed after repeated passage in cell culture or through animals<sup><a id=\"ref-link-section-d6507832e653\" title=\"Ito, T. et al. J. Virol. 75, 4439\u20134443 (2001).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR17\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 17\">17<\/a><\/sup>.<\/strong><\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The function of the predicted O-linked glycans is unclear, but they could create a \u2018mucin-like domain\u2019 that shields epitopes or key residues on the SARS-CoV-2 spike protein<sup><a id=\"ref-link-section-d6507832e660\" title=\"Bagdonaite, I. &amp; Wandall, H. H. Glycobiology 28, 443\u2013467 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR18\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 18\">18<\/a><\/sup>. Several viruses utilize mucin-like domains as glycan shields involved immunoevasion<sup><a id=\"ref-link-section-d6507832e664\" title=\"Bagdonaite, I. &amp; Wandall, H. H. Glycobiology 28, 443\u2013467 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR18\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 18\">18<\/a><\/sup>. Although prediction of O-linked glycosylation is robust, experimental studies are needed to determine if these sites are used in SARS-CoV-2.<\/span><\/p>\n<\/div>\n<\/div>\n<\/section>\n<section data-title=\"Theories of SARS-CoV-2 origins\">\n<div id=\"Sec4-section\" class=\"c-article-section\">\n<h2 id=\"Sec4\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Theories of SARS-CoV-2 origins<\/h2>\n<div id=\"Sec4-content\" class=\"c-article-section__content\">\n<p><span style=\"font-size: 14pt;\">It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution different from those previously predicted<sup><a id=\"ref-link-section-d6507832e677\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a>,<a id=\"ref-link-section-d6507832e680\" title=\"Sheahan, T. et al. J. Virol. 82, 2274\u20132285 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR11\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\">11<\/a><\/sup>. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used<sup><a id=\"ref-link-section-d6507832e684\" title=\"Cui, J., Li, F. &amp; Shi, Z.-L. Nat. Rev. Microbiol. 17, 181\u2013192 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR19\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 19\">19<\/a><\/sup>. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone<sup><a id=\"ref-link-section-d6507832e688\" title=\"Almaz\u00e1n, F. et al. Virus Res. 189, 262\u2013270 (2014).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR20\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 20\">20<\/a><\/sup>. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage could have given rise to SARS-CoV-2.<\/span><\/p>\n<h3 id=\"Sec5\" class=\"c-article__sub-heading\">1. Natural selection in an animal host before zoonotic transfer<\/h3>\n<p><span style=\"font-size: 14pt;\">As many early cases of COVID-19 were linked to the Huanan market in Wuhan<sup><a id=\"ref-link-section-d6507832e699\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e702\" title=\"Wu, F. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>, it is possible that an animal source was present at this location. Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses<sup><a id=\"ref-link-section-d6507832e706\" title=\"Wu, F. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>, it is likely that bats serve as reservoir hosts for its progenitor. Although RaTG13, sampled from a <i>Rhinolophus affinis<\/i> bat<sup><a id=\"ref-link-section-d6507832e713\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a><\/sup>, is ~96% identical overall to SARS-CoV-2, its spike diverges in the RBD, which suggests that it may not bind efficiently to human ACE2<sup><a id=\"ref-link-section-d6507832e717\" title=\"Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. J. Virol. https:\/\/doi.org\/10.1128\/JVI.00127-20 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR7\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\">7<\/a><\/sup> (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1a<\/a>).<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Malayan pangolins (<i>Manis javanica<\/i>) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2<sup><a id=\"ref-link-section-d6507832e731\" title=\"Zhang, T., Wu, Q. &amp; Zhang, Z. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.950253 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR21\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 21\">21<\/a><\/sup>. Although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome<sup><a id=\"ref-link-section-d6507832e735\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a><\/sup>, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the RBD, including all six key RBD residues<sup><a id=\"ref-link-section-d6507832e739\" title=\"Zhang, T., Wu, Q. &amp; Zhang, Z. bioRxiv https:\/\/doi.org\/10.1101\/2020.02.19.950253 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR21\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 21\">21<\/a><\/sup> (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1<\/a>). This clearly shows that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2 <strong>is the result of natural selection.<\/strong><\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. Mutations, insertions and deletions can occur near the S1\u2013S2 junction of coronaviruses<sup><a id=\"ref-link-section-d6507832e749\" title=\"Yamada, Y. &amp; Liu, D. X. J. Virol. 83, 8744\u20138758 (2009).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR22\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 22\">22<\/a><\/sup>, which shows that the polybasic cleavage site can arise by a natural evolutionary process. For a precursor virus to acquire both the polybasic cleavage site and mutations in the spike protein suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog.<\/span><\/p>\n<h3 id=\"Sec6\" class=\"c-article__sub-heading\">2. Natural selection in humans following zoonotic transfer<\/h3>\n<p><span style=\"font-size: 14pt;\">It is possible that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described above through adaptation during undetected human-to-human transmission. Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases to trigger the surveillance system that detected it<sup><a id=\"ref-link-section-d6507832e761\" title=\"Zhou, P. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR1\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 1\">1<\/a>,<a id=\"ref-link-section-d6507832e764\" title=\"Wu, F. et al. Nature https:\/\/doi.org\/10.1038\/s41586-020-2008-3 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR2\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 2\">2<\/a><\/sup>.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">All SARS-CoV-2 genomes sequenced so far have the genomic features described above and are thus derived from a common ancestor that had them too. The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. This leaves the insertion of polybasic cleavage site to occur during human-to-human transmission.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Estimates of the timing of the most recent common ancestor of SARS-CoV-2 made with current sequence data point to emergence of the virus in late November 2019 to early December 2019<sup><a id=\"ref-link-section-d6507832e774\" title=\"Rambaut, A. Virological.org http:\/\/virological.org\/t\/356 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR23\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 23\">23<\/a><\/sup>, compatible with the earliest retrospectively confirmed cases<sup><a id=\"ref-link-section-d6507832e778\" title=\"Huang, C. et al. Lancet https:\/\/doi.org\/10.1016\/S0140-6736(20)30183-5 (2020).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR24\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 24\">24<\/a><\/sup>. Hence, this scenario presumes a period of unrecognized transmission in humans between the initial zoonotic event and the acquisition of the polybasic cleavage site. Sufficient opportunity could have arisen if there had been many prior zoonotic events that produced short chains of human-to-human transmission over an extended period. This is essentially the situation for MERS-CoV, for which all human cases are the result of repeated jumps of the virus from dromedary camels, producing single infections or short transmission chains that eventually resolve, with no adaptation to sustained transmission<sup><a id=\"ref-link-section-d6507832e782\" title=\"Dudas, G., Carvalho, L. M., Rambaut, A. &amp; Bedford, T. eLife 7, e31257 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR25\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 25\">25<\/a><\/sup>.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Studies of banked human samples could provide information on whether such cryptic spread has occurred. Retrospective serological studies could also be informative, and a few such studies have been conducted showing low-level exposures to SARS-CoV-like coronaviruses in certain areas of China<sup><a id=\"ref-link-section-d6507832e789\" title=\"Wang, N. et al. Virol. Sin. 33, 104\u2013107 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR26\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 26\">26<\/a><\/sup>. Critically, however, these studies could not have distinguished whether exposures were due to prior infections with SARS-CoV, SARS-CoV-2 or other SARS-CoV-like coronaviruses. Further serological studies should be conducted to determine the extent of prior human exposure to SARS-CoV-2.<\/span><\/p>\n<h3 id=\"Sec7\" class=\"c-article__sub-heading\">3. Selection during passage<\/h3>\n<p><span style=\"font-size: 14pt;\">Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and\/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world<sup><a id=\"ref-link-section-d6507832e801\" title=\"Ge, X.-Y. et al. Nature 503, 535\u2013538 (2013).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR27\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 27\">27<\/a><\/sup>, and there are documented instances of laboratory escapes of SARS-CoV<sup><a id=\"ref-link-section-d6507832e805\" title=\"Lim, P. L. et al. N. Engl. J. Med. 350, 1740\u20131745 (2004).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR28\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 28\">28<\/a><\/sup>. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. <a href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#Fig1\" data-track=\"click\" data-track-label=\"link\" data-track-action=\"figure anchor\">1a<\/a>) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV<sup><a id=\"ref-link-section-d6507832e815\" title=\"Sheahan, T. et al. J. Virol. 82, 2274\u20132285 (2008).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR11\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\">11<\/a><\/sup>. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation<sup><a id=\"ref-link-section-d6507832e819\" title=\"Cui, J., Li, F. &amp; Shi, Z.-L. Nat. Rev. Microbiol. 17, 181\u2013192 (2019).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR19\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 19\">19<\/a><\/sup>.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo<sup><a id=\"ref-link-section-d6507832e826\" title=\"Ito, T. et al. J. Virol. 75, 4439\u20134443 (2001).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR17\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 17\">17<\/a><\/sup>. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system<sup><a id=\"ref-link-section-d6507832e830\" title=\"Bagdonaite, I. &amp; Wandall, H. H. Glycobiology 28, 443\u2013467 (2018).\" href=\"https:\/\/www.nature.com\/articles\/s41591-020-0820-9#ref-CR18\" data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 18\">18<\/a><\/sup>.<\/span><\/p>\n<\/div>\n<\/div>\n<\/section>\n<section data-title=\"Conclusions\">\n<div id=\"Sec8-section\" class=\"c-article-section\">\n<h2 id=\"Sec8\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Conclusions<\/h2>\n<div id=\"Sec8-content\" class=\"c-article-section__content\">\n<p><span style=\"font-size: 14pt;\">In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. <strong>Detailed understanding of how an animal virus jumped species boundaries to infect humans so productively will help in the prevention of future zoonotic events.<\/strong> For example, if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events. In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations. In addition, identifying the closest viral relatives of SARS-CoV-2 circulating in animals will greatly assist studies of viral function. Indeed, the availability of the RaTG13 bat sequence helped reveal key RBD mutations and the polybasic cleavage site.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The genomic features described here may explain in part the infectiousness and transmissibility of SARS-CoV-2 in humans. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here. However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">More scientific data could swing the balance of evidence to favor one hypothesis over another. Obtaining related viral sequences from animal sources would be the most definitive way of revealing viral origins. For example, a future observation of an intermediate or fully formed polybasic cleavage site in a SARS-CoV-2-like virus from animals would lend even further support to the natural-selection hypotheses. It would also be helpful to obtain more genetic and functional data about SARS-CoV-2, including animal studies. The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.<\/span><\/p>\n<\/div>\n<\/div>\n<\/section>\n<div id=\"MagazineFulltextArticleBodySuffix\">\n<section aria-labelledby=\"Bib1\" data-title=\"References\">\n<div id=\"Bib1-section\" class=\"c-article-section\">\n<h2 id=\"Bib1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">References<\/h2>\n<div id=\"Bib1-content\" class=\"c-article-section__content\">\n<div data-container-section=\"references\">\n<ol class=\"c-article-references\">\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">1.<\/span>\n<p id=\"ref-CR1\" class=\"c-article-references__text\">Zhou, P. et al. <i>Nature<\/i> <a href=\"https:\/\/doi.org\/10.1038\/s41586-020-2012-7\">https:\/\/doi.org\/10.1038\/s41586-020-2012-7<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1038%2Fs41586-020-2012-7\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 1\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32269352\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 1\">PubMed<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7095418\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed Central reference 1\">PubMed Central<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Nature&amp;doi=10.1038%2Fs41586-020-2012-7&amp;publication_year=2020&amp;author=Zhou%2CP\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 1\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">2.<\/span>\n<p id=\"ref-CR2\" class=\"c-article-references__text\">Wu, F. et al. <i>Nature<\/i> <a href=\"https:\/\/doi.org\/10.1038\/s41586-020-2008-3\">https:\/\/doi.org\/10.1038\/s41586-020-2008-3<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1038%2Fs41586-020-2008-3\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 2\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32269338\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 2\">PubMed<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7094943\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed Central reference 2\">PubMed Central<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Nature&amp;doi=10.1038%2Fs41586-020-2008-3&amp;publication_year=2020&amp;author=Wu%2CF\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 2\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">3.<\/span>\n<p id=\"ref-CR3\" class=\"c-article-references__text\">Gorbalenya, A. E. et al. <i>bioRxiv<\/i> <a href=\"https:\/\/doi.org\/10.1101\/2020.02.07.937862\">https:\/\/doi.org\/10.1101\/2020.02.07.937862<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1101%2F2020.02.07.937862\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 3\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=bioRxiv&amp;doi=10.1101%2F2020.02.07.937862&amp;publication_year=2020&amp;author=Gorbalenya%2CAE\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 3\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">4.<\/span>\n<p id=\"ref-CR4\" class=\"c-article-references__text\">Jiang, S. et al. <i>Lancet<\/i> <a href=\"https:\/\/doi.org\/10.1016\/S0140-6736(20)30419-0\">https:\/\/doi.org\/10.1016\/S0140-6736(20)30419-0<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1016%2FS0140-6736%2820%2930419-0\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 4\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32272084\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 4\">PubMed<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7124694\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed Central reference 4\">PubMed Central<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Lancet&amp;doi=10.1016%2FS0140-6736%2820%2930419-0&amp;publication_year=2020&amp;author=Jiang%2CS\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 4\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">5.<\/span>\n<p id=\"ref-CR5\" class=\"c-article-references__text\">Dong, E., Du, H. &amp; Gardner, L. <i>Lancet Infect. Dis.<\/i> <a href=\"https:\/\/doi.org\/10.1016\/S1473-3099(20)30120-1\">https:\/\/doi.org\/10.1016\/S1473-3099(20)30120-1<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1016%2FS1473-3099%2820%2930120-1\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 5\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32087114\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 5\">PubMed<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Lancet%20Infect.%20Dis.&amp;doi=10.1016%2FS1473-3099%2820%2930120-1&amp;publication_year=2020&amp;author=Dong%2CE&amp;author=Du%2CH&amp;author=Gardner%2CL\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 5\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">6.<\/span>\n<p id=\"ref-CR6\" class=\"c-article-references__text\">Corman, V. M., Muth, D., Niemeyer, D. &amp; Drosten, C. <i>Adv. Virus Res.<\/i> <b>100<\/b>, 163\u2013188 (2018).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1016%2Fbs.aivir.2018.01.001\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 6\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Adv.%20Virus%20Res.&amp;volume=100&amp;pages=163-188&amp;publication_year=2018&amp;author=Corman%2CVM&amp;author=Muth%2CD&amp;author=Niemeyer%2CD&amp;author=Drosten%2CC\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 6\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">7.<\/span>\n<p id=\"ref-CR7\" class=\"c-article-references__text\">Wan, Y., Shang, J., Graham, R., Baric, R. S. &amp; Li, F. <i>J. Virol.<\/i> <a href=\"https:\/\/doi.org\/10.1128\/JVI.00127-20\">https:\/\/doi.org\/10.1128\/JVI.00127-20<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1128%2FJVI.00127-20\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 7\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=31996437\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 7\">PubMed<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=J.%20Virol.&amp;doi=10.1128%2FJVI.00127-20&amp;publication_year=2020&amp;author=Wan%2CY&amp;author=Shang%2CJ&amp;author=Graham%2CR&amp;author=Baric%2CRS&amp;author=Li%2CF\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 7\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">8.<\/span>\n<p id=\"ref-CR8\" class=\"c-article-references__text\">Walls, A. C. et al. <i>bioRxiv<\/i> <a href=\"https:\/\/doi.org\/10.1101\/2020.02.19.956581\">https:\/\/doi.org\/10.1101\/2020.02.19.956581<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1101%2F2020.02.19.956581\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 8\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=bioRxiv&amp;doi=10.1101%2F2020.02.19.956581&amp;publication_year=2020&amp;author=Walls%2CAC\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 8\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">9.<\/span>\n<p id=\"ref-CR9\" class=\"c-article-references__text\">Wrapp, D. et al. <i>Science<\/i> <a href=\"https:\/\/doi.org\/10.1126\/science.abb2507\">https:\/\/doi.org\/10.1126\/science.abb2507<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1126%2Fscience.abb2507\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 9\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32075877\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 9\">PubMed<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Science&amp;doi=10.1126%2Fscience.abb2507&amp;publication_year=2020&amp;author=Wrapp%2CD\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 9\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">10.<\/span>\n<p id=\"ref-CR10\" class=\"c-article-references__text\">Letko, M., Marzi, A. &amp; Munster, V. <i>Nat. Microbiol.<\/i> <a href=\"https:\/\/doi.org\/10.1038\/s41564-020-0688-y\">https:\/\/doi.org\/10.1038\/s41564-020-0688-y<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1038%2Fs41564-020-0688-y\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 10\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32094589\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 10\">PubMed<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7095430\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed Central reference 10\">PubMed Central<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Nat.%20Microbiol.&amp;doi=10.1038%2Fs41564-020-0688-y&amp;publication_year=2020&amp;author=Letko%2CM&amp;author=Marzi%2CA&amp;author=Munster%2CV\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 10\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">11.<\/span>\n<p id=\"ref-CR11\" class=\"c-article-references__text\">Sheahan, T. et al. <i>J. Virol.<\/i> <b>82<\/b>, 2274\u20132285 (2008).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD1cXitlyhtLY%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 11\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1128%2FJVI.02041-07\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 11\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=J.%20Virol.&amp;volume=82&amp;pages=2274-2285&amp;publication_year=2008&amp;author=Sheahan%2CT\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 11\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">12.<\/span>\n<p id=\"ref-CR12\" class=\"c-article-references__text\">Nao, N. et al. <i>MBio<\/i> <b>8<\/b>, e02298-16 (2017).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1128%2FmBio.02298-16\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 12\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=MBio&amp;volume=8&amp;publication_year=2017&amp;author=Nao%2CN\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 12\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">13.<\/span>\n<p id=\"ref-CR13\" class=\"c-article-references__text\">Chan, C.-M. et al. <i>Exp. Biol. Med.<\/i> <b>233<\/b>, 1527\u20131536 (2008).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD1cXhsVOjtLjK\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 13\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.3181%2F0806-RM-197\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 13\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Exp.%20Biol.%20Med.&amp;volume=233&amp;pages=1527-1536&amp;publication_year=2008&amp;author=Chan%2CC-M\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 13\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">14.<\/span>\n<p id=\"ref-CR14\" class=\"c-article-references__text\">Follis, K. E., York, J. &amp; Nunberg, J. H. <i>Virology<\/i> <b>350<\/b>, 358\u2013369 (2006).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD28Xmt1Gkt7c%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 14\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1016%2Fj.virol.2006.02.003\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 14\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Virology&amp;volume=350&amp;pages=358-369&amp;publication_year=2006&amp;author=Follis%2CKE&amp;author=York%2CJ&amp;author=Nunberg%2CJH\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 14\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">15.<\/span>\n<p id=\"ref-CR15\" class=\"c-article-references__text\">Menachery, V. D. et al. <i>J. Virol.<\/i> <a href=\"https:\/\/doi.org\/10.1128\/JVI.01774-19\">https:\/\/doi.org\/10.1128\/JVI.01774-19<\/a> (2019).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1128%2FJVI.01774-19\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 15\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=31462558\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 15\">PubMed<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=J.%20Virol.&amp;doi=10.1128%2FJVI.01774-19&amp;publication_year=2019&amp;author=Menachery%2CVD\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 15\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">16.<\/span>\n<p id=\"ref-CR16\" class=\"c-article-references__text\">Alexander, D. J. &amp; Brown, I. H. <i>Rev. Sci. Tech.<\/i> <b>28<\/b>, 19\u201338 (2009).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ASTN%3A280%3ADC%252BD1Mvps1CktQ%253D%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 16\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.20506%2Frst.28.1.1856\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 16\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Rev.%20Sci.%20Tech.&amp;volume=28&amp;pages=19-38&amp;publication_year=2009&amp;author=Alexander%2CDJ&amp;author=Brown%2CIH\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 16\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">17.<\/span>\n<p id=\"ref-CR17\" class=\"c-article-references__text\">Ito, T. et al. <i>J. Virol.<\/i> <b>75<\/b>, 4439\u20134443 (2001).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD3MXivFOkur0%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 17\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1128%2FJVI.75.9.4439-4443.2001\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 17\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=J.%20Virol.&amp;volume=75&amp;pages=4439-4443&amp;publication_year=2001&amp;author=Ito%2CT\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 17\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">18.<\/span>\n<p id=\"ref-CR18\" class=\"c-article-references__text\">Bagdonaite, I. &amp; Wandall, H. H. <i>Glycobiology<\/i> <b>28<\/b>, 443\u2013467 (2018).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BC1MXht1Witb7L\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 18\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1093%2Fglycob%2Fcwy021\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 18\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Glycobiology&amp;volume=28&amp;pages=443-467&amp;publication_year=2018&amp;author=Bagdonaite%2CI&amp;author=Wandall%2CHH\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 18\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">19.<\/span>\n<p id=\"ref-CR19\" class=\"c-article-references__text\">Cui, J., Li, F. &amp; Shi, Z.-L. <i>Nat. Rev. Microbiol.<\/i> <b>17<\/b>, 181\u2013192 (2019).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BC1cXisVyhtbnL\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 19\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1038%2Fs41579-018-0118-9\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 19\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Nat.%20Rev.%20Microbiol.&amp;volume=17&amp;pages=181-192&amp;publication_year=2019&amp;author=Cui%2CJ&amp;author=Li%2CF&amp;author=Shi%2CZ-L\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 19\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">20.<\/span>\n<p id=\"ref-CR20\" class=\"c-article-references__text\">Almaz\u00e1n, F. et al. <i>Virus Res.<\/i> <b>189<\/b>, 262\u2013270 (2014).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1016%2Fj.virusres.2014.05.026\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 20\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Virus%20Res.&amp;volume=189&amp;pages=262-270&amp;publication_year=2014&amp;author=Almaz%C3%A1n%2CF\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 20\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">21.<\/span>\n<p id=\"ref-CR21\" class=\"c-article-references__text\">Zhang, T., Wu, Q. &amp; Zhang, Z. <i>bioRxiv<\/i> <a href=\"https:\/\/doi.org\/10.1101\/2020.02.19.950253\">https:\/\/doi.org\/10.1101\/2020.02.19.950253<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1101%2F2020.02.19.950253\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 21\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=bioRxiv&amp;doi=10.1101%2F2020.02.19.950253&amp;publication_year=2020&amp;author=Zhang%2CT&amp;author=Wu%2CQ&amp;author=Zhang%2CZ\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 21\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">22.<\/span>\n<p id=\"ref-CR22\" class=\"c-article-references__text\">Yamada, Y. &amp; Liu, D. X. <i>J. Virol.<\/i> <b>83<\/b>, 8744\u20138758 (2009).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD1MXhtFahurvL\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 22\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1128%2FJVI.00613-09\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 22\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=J.%20Virol.&amp;volume=83&amp;pages=8744-8758&amp;publication_year=2009&amp;author=Yamada%2CY&amp;author=Liu%2CDX\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 22\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">23.<\/span>\n<p id=\"ref-CR23\" class=\"c-article-references__text\">Rambaut, A. <i>Virological.org<\/i> <a href=\"http:\/\/virological.org\/t\/356\">http:\/\/virological.org\/t\/356<\/a> (2020).<\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">24.<\/span>\n<p id=\"ref-CR24\" class=\"c-article-references__text\">Huang, C. et al. <i>Lancet<\/i> <a href=\"https:\/\/doi.org\/10.1016\/S0140-6736(20)30183-5\">https:\/\/doi.org\/10.1016\/S0140-6736(20)30183-5<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1016%2FS0140-6736%2820%2930183-5\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 24\">Article<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/entrez\/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Abstract&amp;list_uids=32243822\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed reference 24\">PubMed<\/a>\u00a0 <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7133598\" rel=\"nofollow\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"PubMed Central reference 24\">PubMed Central<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Lancet&amp;doi=10.1016%2FS0140-6736%2820%2930183-5&amp;publication_year=2020&amp;author=Huang%2CC\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 24\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">25.<\/span>\n<p id=\"ref-CR25\" class=\"c-article-references__text\">Dudas, G., Carvalho, L. M., Rambaut, A. &amp; Bedford, T. <i>eLife<\/i> <b>7<\/b>, e31257 (2018).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.7554%2FeLife.31257\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 25\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=eLife&amp;volume=7&amp;publication_year=2018&amp;author=Dudas%2CG&amp;author=Carvalho%2CLM&amp;author=Rambaut%2CA&amp;author=Bedford%2CT\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 25\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">26.<\/span>\n<p id=\"ref-CR26\" class=\"c-article-references__text\">Wang, N. et al. <i>Virol. Sin.<\/i> <b>33<\/b>, 104\u2013107 (2018).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1007%2Fs12250-018-0012-7\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 26\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Virol.%20Sin.&amp;volume=33&amp;pages=104-107&amp;publication_year=2018&amp;author=Wang%2CN\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 26\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">27.<\/span>\n<p id=\"ref-CR27\" class=\"c-article-references__text\">Ge, X.-Y. et al. <i>Nature<\/i> <b>503<\/b>, 535\u2013538 (2013).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BC3sXhslSnsLrF\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 27\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1038%2Fnature12711\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 27\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Nature&amp;volume=503&amp;pages=535-538&amp;publication_year=2013&amp;author=Ge%2CX-Y\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 27\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">28.<\/span>\n<p id=\"ref-CR28\" class=\"c-article-references__text\">Lim, P. L. et al. <i>N. Engl. J. Med.<\/i> <b>350<\/b>, 1740\u20131745 (2004).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BD2cXjt12murs%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 28\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.1056%2FNEJMoa032565\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 28\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=N.%20Engl.%20J.%20Med.&amp;volume=350&amp;pages=1740-1745&amp;publication_year=2004&amp;author=Lim%2CPL\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 28\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">29.<\/span>\n<p id=\"ref-CR29\" class=\"c-article-references__text\">Wong, M. C., Javornik Cregeen, S. J., Ajami, N. J. &amp; Petrosino, J. F. <i>bioRxiv<\/i> <a href=\"https:\/\/doi.org\/10.1101\/2020.02.07.939207\">https:\/\/doi.org\/10.1101\/2020.02.07.939207<\/a> (2020).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/doi.org\/10.1101%2F2020.02.07.939207\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 29\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=bioRxiv&amp;doi=10.1101%2F2020.02.07.939207&amp;publication_year=2020&amp;author=Wong%2CMC&amp;author=Javornik%20Cregeen%2CSJ&amp;author=Ajami%2CNJ&amp;author=Petrosino%2CJF\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 29\"> Google Scholar<\/a><\/p>\n<\/li>\n<li class=\"c-article-references__item js-c-reading-companion-references-item\"><span class=\"c-article-references__counter\">30.<\/span>\n<p id=\"ref-CR30\" class=\"c-article-references__text\">Liu, P., Chen, W. &amp; Chen, J.-P. <i>Viruses<\/i> <b>11<\/b>, 979 (2019).<\/p>\n<p class=\"c-article-references__links u-hide-print\"><a href=\"https:\/\/www.nature.com\/articles\/cas-redirect\/1%3ACAS%3A528%3ADC%252BB3cXmsFeitbk%253D\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"CAS reference 30\">CAS<\/a>\u00a0 <a href=\"https:\/\/doi.org\/10.3390%2Fv11110979\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Article reference 30\">Article<\/a>\u00a0 <a href=\"http:\/\/scholar.google.com\/scholar_lookup?&amp;title=&amp;journal=Viruses&amp;volume=11&amp;publication_year=2019&amp;author=Liu%2CP&amp;author=Chen%2CW&amp;author=Chen%2CJ-P\" data-track=\"click\" data-track-action=\"outbound reference\" data-track-label=\"link\" aria-label=\"Google Scholar reference 30\"> Google Scholar<\/a><\/p>\n<\/li>\n<\/ol>\n<p class=\"c-article-references__download u-hide-print\"><a href=\"https:\/\/citation-needed.springer.com\/v2\/references\/10.1038\/s41591-020-0820-9?format=refman&amp;flavour=references\" data-track=\"click\" data-track-action=\"download citation references\" data-track-label=\"link\">Download references<\/a><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n<\/div>\n<section data-title=\"Acknowledgements\">\n<div id=\"Ack1-section\" class=\"c-article-section\">\n<h2 id=\"Ack1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Acknowledgements<\/h2>\n<div id=\"Ack1-content\" class=\"c-article-section__content\">\n<p>We thank all those who have contributed sequences to the GISAID database (<a href=\"https:\/\/www.gisaid.org\/\">https:\/\/www.gisaid.org\/<\/a>) and analyses to Virological.org (<a href=\"http:\/\/virological.org\/\">http:\/\/virological.org\/<\/a>). We thank M. Farzan for discussions, and the Wellcome Trust for support. K.G.A. is a Pew Biomedical Scholar and is supported by NIH grant U19AI135995. A.R. is supported by the Wellcome Trust (Collaborators Award 206298\/Z\/17\/Z\u2015ARTIC network) and the European Research Council (grant agreement no. 725422\u2015ReservoirDOCS). E.C.H. is supported by an ARC Australian Laureate Fellowship (FL170100022). R.F.G. is supported by NIH grants U19AI135995, U54 HG007480 and U19AI142790.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<section aria-labelledby=\"author-information\" data-title=\"Author information\">\n<div id=\"author-information-section\" class=\"c-article-section\">\n<h2 id=\"author-information\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Author information<\/h2>\n<div id=\"author-information-content\" class=\"c-article-section__content\">\n<h3 id=\"affiliations\" class=\"c-article__sub-heading\">Affiliations<\/h3>\n<ol class=\"c-article-author-affiliation__list\">\n<li id=\"Aff1\">\n<p class=\"c-article-author-affiliation__address\">Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Kristian G. Andersen<\/p>\n<\/li>\n<li id=\"Aff2\">\n<p class=\"c-article-author-affiliation__address\">Scripps Research Translational Institute, La Jolla, CA, USA<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Kristian G. Andersen<\/p>\n<\/li>\n<li id=\"Aff3\">\n<p class=\"c-article-author-affiliation__address\">Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Andrew Rambaut<\/p>\n<\/li>\n<li id=\"Aff4\">\n<p class=\"c-article-author-affiliation__address\">Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, NY, USA<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">W. Ian Lipkin<\/p>\n<\/li>\n<li id=\"Aff5\">\n<p class=\"c-article-author-affiliation__address\">Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Edward C. Holmes<\/p>\n<\/li>\n<li id=\"Aff6\">\n<p class=\"c-article-author-affiliation__address\">Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Robert F. Garry<\/p>\n<\/li>\n<li id=\"Aff7\">\n<p class=\"c-article-author-affiliation__address\">Zalgen Labs, Germantown, MD, USA<\/p>\n<p class=\"c-article-author-affiliation__authors-list\">Robert F. Garry<\/p>\n<\/li>\n<\/ol>\n<h3 id=\"corresponding-author\" class=\"c-article__sub-heading\">Corresponding author<\/h3>\n<p id=\"corresponding-author-list\">Correspondence to Kristian G. Andersen.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<section data-title=\"Ethics declarations\">\n<div id=\"ethics-section\" class=\"c-article-section\">\n<h2 id=\"ethics\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Ethics declarations<\/h2>\n<div id=\"ethics-content\" class=\"c-article-section__content\">\n<h3 id=\"FPar1\" class=\"c-article__sub-heading\">Competing interests<\/h3>\n<p>R.F.G. is co-founder of Zalgen Labs, a biotechnology company that develops countermeasures to emerging viruses.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<section data-title=\"Rights and permissions\">\n<div id=\"rightslink-section\" class=\"c-article-section\">\n<h2 id=\"rightslink\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Rights and permissions<\/h2>\n<p><strong><span style=\"font-size: 18pt;\">\u03a3.\u03b3.: \u039c\u03b5 \u03c4\u03bf \u03c0\u03b9\u03bf \u03c0\u03ac\u03bd\u03c9 \u03ac\u03c1\u03b8\u03c1\u03bf \u03cc\u03bb\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c4\u03b1\u03ba\u03c4\u03bf\u03c0\u03bf\u03b9\u03b7\u03bc\u03ad\u03bd\u03b1, \u03bf\u03b9 \u03ba\u03c5\u03b2\u03b5\u03c1\u03bd\u03ae\u03c3\u03b5\u03b9\u03c2 \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03c4\u03bf \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03bf\u03cd\u03bd \u03b3\u03b9\u03b1 \u03c4\u03bf \u03ba\u03b1\u03bb\u03cc \u03bc\u03b1\u03c2, \u03bf\u03b9 \u03b3\u03b9\u03b1\u03c4\u03c1\u03bf\u03af \u03b3\u03b9\u03b1 \u03bd\u03b1 \u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03bf\u03cd\u03bd \u03c4\u03bf\u03bd \u03b5\u03bc\u03b2\u03bf\u03bb\u03b9\u03b1\u03c3\u03bc\u03cc \u03cc\u03bb\u03c9\u03bd \u03bc\u03b1\u03c2 \u03b3\u03b9\u03b1 \u03bd\u03b1 &#8220;\u03c3\u03c9\u03b8\u03bf\u03cd\u03bc\u03b5&#8221; \u03ba\u03b1\u03b9 \u03cc\u03c3\u03bf\u03b9 \u03c0\u03b5\u03b8\u03b1\u03af\u03bd\u03bf\u03c5\u03bd \u03b1\u03c0\u03cc \u03c4\u03b9\u03c2 \u03c0\u03b1\u03c1\u03b5\u03bd\u03ad\u03c1\u03b3\u03b5\u03b9\u03b5\u03c2 \u03c4\u03bf\u03c5 &#8220;\u03c4\u03c3\u03b9\u03bc\u03c0\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2&#8221;, \u03b1\u03c5\u03c4\u03cc \u00a8\u03bf\u03c6\u03b5\u03af\u03bb\u03b5\u03c4\u03b1\u03b9 \u03c3\u03b5 \u03ac\u03bb\u03bb\u03b5\u03c2 \u03b1\u03b9\u03c4\u03af\u03b5\u03c2&#8221;\u00a0 \u03c0\u03bb\u03b7\u03bd \u03c4\u03c9\u03bd \u03b5\u03bc\u03b2\u03bf\u03bb\u03af\u03c9\u03bd. \u0394\u03b5\u03af\u03c4\u03b5 \u03c4\u03b7\u03bd \u03c0\u03b1\u03c1\u03b1\u03ba\u03ac\u03c4\u03c9 \u03b1\u03bd\u03ac\u03c1\u03c4\u03b7\u03c3\u03b7:<\/span><\/strong><\/p>\n<\/div>\n<\/section>\n<\/div>\n<\/article>\n","protected":false},"excerpt":{"rendered":"<p>\u03a4\u03bf \u03c0\u03b1\u03c1\u03b1\u03ba\u03ac\u03c4\u03c9 \u03ac\u03c1\u03b8\u03c1\u03bf \u03ad\u03ba\u03b1\u03bd\u03b5 \u03b5\u03bd\u03c4\u03cd\u03c0\u03c9\u03c3\u03b7 \u03bf\u03bb\u03bf\u03c3\u03c7\u03b5\u03c1\u03ce\u03c2 \u03b1\u03c1\u03bd\u03b7\u03c4\u03b9\u03ba\u03ae \u03c3\u03c4\u03b7\u03bd \u03b9\u03b1\u03c4\u03c1\u03cc , \u03b5\u03c1\u03b5\u03c5\u03bd\u03ae\u03c4\u03b9\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c5\u03b3\u03b3\u03c1\u03b1\u03c6\u03ad\u03b1 Meryl Nass \u03b7 \u03bf\u03c0\u03bf\u03af\u03b1 \u03c4\u03bf \u03b2\u03c1\u03ae\u03ba\u03b5 \u03cc\u03c7\u03b9 \u03b1\u03c0\u03bb\u03ce\u03c2 \u03b1\u03c4\u03b5\u03bb\u03ad\u03c2 \u03b1\u03bb\u03bb\u03ac \u03cc\u03c4\u03b9 \u03ba\u03ac\u03c4\u03b9 \u03b4\u03b5\u03bd \u03c0\u03ae\u03b3\u03b1\u03b9\u03bd\u03b5 \u03ba\u03b1\u03b9 \u03b1\u03bd\u03b1\u03c1\u03c9\u03c4\u03ae\u03b8\u03b7\u03ba\u03b5 \u03c0\u03c9\u03c2 \u03c4\u03cc\u03c3\u03bf\u03c5 \u03b5\u03c5\u03b7\u03c0\u03cc\u03bb\u03b7\u03c0\u03c4\u03bf\u03b9 \u03ba\u03b1\u03b9 \u03ba\u03b1\u03c4\u03b1\u03be\u03b9\u03c9\u03bc\u03ad\u03bd\u03bf\u03b9 \u03c3\u03c5\u03bd\u03ac\u03b4\u03b5\u03bb\u03c6\u03bf\u03b9 \u03ae\u03c4\u03b1\u03bd \u03b4\u03c5\u03bd\u03b1\u03c4\u03cc\u03bd \u03bd\u03b1 \u03c7\u03c1\u03b7\u03c3\u03b9\u03bc\u03bf\u03c0\u03bf\u03b9\u03ae\u03c3\u03bf\u03c5\u03bd \u03b1\u03c5\u03c4\u03cc \u03c4\u03bf \u03ac\u03c1\u03b8\u03c1\u03bf \u03b3\u03b9\u03b1 \u03bd\u03b1 \u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03ae\u03c3\u03bf\u03c5\u03bd \u03ba\u03b1\u03b9 \u03bd\u03b1 \u03b4\u03b9\u03ba\u03b1\u03b9\u03bf\u03bb\u03bf\u03b3\u03bf\u03cd\u03bd \u03bc\u03ad\u03c7\u03c1\u03b9 \u03c3\u03ae\u03bc\u03b5\u03c1\u03b1 \u03ba\u03ac\u03c4\u03b9 \u03c0\u03bf\u03c5 \u03ae\u03c4\u03b1\u03bd \u03b5\u03be \u03b1\u03c1\u03c7\u03ae\u03c2 &hellip; <\/p>\n<p><a class=\"more-link btn\" href=\"https:\/\/evaggelatos.com\/?p=23274\">\u03a3\u03c5\u03bd\u03ad\u03c7\u03b5\u03b9\u03b1 \u03b1\u03bd\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7\u03c2<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[85],"tags":[90],"class_list":["post-23274","post","type-post","status-publish","format-standard","hentry","category-85","tag-90","item-wrap"],"_links":{"self":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23274","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=23274"}],"version-history":[{"count":7,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23274\/revisions"}],"predecessor-version":[{"id":23281,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23274\/revisions\/23281"}],"wp:attachment":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=23274"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=23274"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=23274"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}