{"id":105185,"date":"2020-04-11T17:47:54","date_gmt":"2020-04-12T00:47:54","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2020\/04\/structure-of-the-rna-dependent-rna-polymerase-from-covid-19-virus"},"modified":"2020-04-11T17:47:54","modified_gmt":"2020-04-12T00:47:54","slug":"structure-of-the-rna-dependent-rna-polymerase-from-covid-19-virus","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2020\/04\/structure-of-the-rna-dependent-rna-polymerase-from-covid-19-virus","title":{"rendered":"Structure of the RNA-dependent RNA polymerase from COVID-19 virus"},"content":{"rendered":"

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A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication\/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-\u00c5 resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified \u03b2-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.<\/p>\n

Corona Virus Disease 2019 (COVID-19) caused by a novel coronavirus emerged in December 2019 (1<\/em><\/a>\u20133<\/em><\/a>) and has since become a global pandemic. COVID-19 virus is reported to be a new member of the betacoronavirus genus and is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV) and to several bat coronaviruses (4<\/em><\/a>). Compared to SARS-CoV and MERS-CoV, COVID-19 virus exhibits faster human-to-human transmission, thus leading to the WHO declaration of a world-wide public health emergency (1<\/em><\/a>, 2<\/em><\/a>).<\/p>\n

CoVs employ a multi-subunit replication\/transcription machinery. A set of non-structural proteins (nsp) produced as cleavage products of the ORF1a and ORF1ab viral polyproteins (5<\/em><\/a>) assemble to facilitate viral replication and transcription. A key component, the RNA-dependent RNA polymerase (RdRp, also known as nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of COVID-19 virus, possibly with the assistance of nsp7 and nsp8 as co-factors (6<\/em><\/a>). Nsp12 is therefore considered a primary target for nucleotide analog antiviral inhibitors such as remdesivir, which shows potential for the treatment of COVID-19 viral infections (7<\/em><\/a>, 8<\/em><\/a>). To inform drug design we have determined the structure of nsp12, in complex with its cofactors nsp7 and nsp8 by cryo-Electron Microscopy (Cryo-EM) using two different protocols, one in the absence of DTT (Dataset-1) and the other in the presence of DTT (Dataset-2).<\/p>\n","protected":false},"excerpt":{"rendered":"

A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication\/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM [\u2026]<\/p>\n","protected":false},"author":396,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,1495],"tags":[],"class_list":["post-105185","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-health"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/105185","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/396"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=105185"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/105185\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=105185"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=105185"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=105185"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}