{"id":3802,"date":"2022-02-03T11:16:01","date_gmt":"2022-02-03T11:16:01","guid":{"rendered":"https:\/\/www.afmb.univ-mrs.fr\/?p=3802"},"modified":"2022-02-10T15:20:46","modified_gmt":"2022-02-10T15:20:46","slug":"les-travaux-de-ahsleigh-shannon-et-lequipe-bruno-canard-sont-mis-a-lhonneur-par-linsb","status":"publish","type":"post","link":"https:\/\/www.afmb.univ-mrs.fr\/en\/2022\/02\/03\/les-travaux-de-ahsleigh-shannon-et-lequipe-bruno-canard-sont-mis-a-lhonneur-par-linsb\/","title":{"rendered":"The work of Ashleigh Shannon and Bruno Canard&#8217;s team highlighted by INSB"},"content":{"rendered":"\n<p><a href=\"https:\/\/www.insb.cnrs.fr\/fr\/cnrsinfo\/le-bemnifosbuvir-527-stoppe-la-replication-du-sars-cov-2-en-ciblant-simultanement-deux\">Lire<\/a><\/p>\n\n\n\n<p>The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). AT-527 recently entered phase III clinical trials for the treatment of COVID-19. Once in cells, AT-527 is converted into its triphosphate form, AT-9010, that presumably targets the viral RNA-dependent RNA polymerase (RdRp, nsp12), for incorporation into viral RNA. Here we report a 2.98\u2009\u00c5 cryo-EM structure of the SARS-CoV-2 nsp12-nsp7-nsp8<sub>2<\/sub>-RNA complex, showing AT-9010 bound at three sites of nsp12. In the RdRp active-site, one AT-9010 is incorporated at the 3\u2032 end of the RNA product strand. Its modified ribose group (2\u2032-fluoro, 2\u2032-methyl) prevents correct alignment of the incoming NTP, in this case a second AT-9010, causing immediate termination of RNA synthesis. The third AT-9010 is bound to the N-terminal domain of nsp12 &#8211; known as the NiRAN. In contrast to native NTPs, AT-9010 is in a flipped orientation in the active-site, with its guanine base unexpectedly occupying a previously unnoticed cavity. AT-9010 outcompetes all native nucleotides for NiRAN binding, inhibiting its nucleotidyltransferase activity. The dual mechanism of action of AT-527 at both RdRp and NiRAN active sites represents a promising research avenue against COVID-19<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Lire The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). AT-527 recently [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":3811,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[9],"class_list":["post-3802","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-informations","entry"],"_links":{"self":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/posts\/3802","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/comments?post=3802"}],"version-history":[{"count":2,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/posts\/3802\/revisions"}],"predecessor-version":[{"id":3815,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/posts\/3802\/revisions\/3815"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/media\/3811"}],"wp:attachment":[{"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/media?parent=3802"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.afmb.univ-mrs.fr\/en\/wp-json\/wp\/v2\/categories?post=3802"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}