Structure of the RNA-dependent RNA polymerase from COVID-19 virus.
Yan Gao,Yan Gao,Liming Yan,Yucen Huang,Fengjiang Liu,Yao Zhao,Lin Cao,Tao Wang,Qianqian Sun,Zhenhua Ming,Lianqi Zhang,Ji Ge,Litao Zheng,Ying Zhang,Haofeng Wang,Haofeng Wang,Yan Zhu,Chen Zhu,Tianyu Hu,Tian Hua,Bing Zhang,Xiuna Yang,Jun Li,Haitao Yang,Zhi-Jie Liu,Wenqing Xu,Luke W. Guddat,Quan Wang,Zhiyong Lou,Zihe Rao +29 more
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TLDR
The structure of the COVID-19 virus polymerase essential for viral replication provides a basis for the design of new antiviral drugs that target viral RdRp, also named nsp12, and it appears to be a primary target for the antiviral drug remdesivir.Abstract:
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-A resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-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.read more
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A pocket guide on how to structure SARS-CoV-2 drugs and therapies.
Dene R. Littler,Dene R. Littler,Bruce J. MacLachlan,Bruce J. MacLachlan,Gabrielle M. Watson,Gabrielle M. Watson,Julian P. Vivian,Julian P. Vivian,Benjamin S. Gully,Benjamin S. Gully +9 more
TL;DR: The contribution of structural studies to the understanding of the SARS-CoV-2 virus and their role in structure-based development of therapeutics is reviewed.
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Potential 3-chymotrypsin-like cysteine protease cleavage sites in the coronavirus polyproteins pp1a and pp1ab and their possible relevance to COVID-19 vaccine and drug development.
Shaomin Yan,Guang Wu +1 more
TL;DR: In this article, the authors investigated the inconsistency in the cleavage sites of 3-chymotrypsin (C)-like cysteine protease (3CLpro) across CoVs, and investigated the function of nsp11.
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SARS-COV-2, infection, transmission, transcription, translation, proteins, and treatment: A review
Jahangir Emrani,Maryam Ahmed,Liesl Jeffers-Francis,John Teleha,Nathan Mowa,Robert H. Newman,Misty D. Thomas +6 more
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Identifying and repurposing antiviral drugs against severe acute respiratory syndrome coronavirus 2 with in silico and in vitro approaches.
TL;DR: This article summarizes the studies using in silico and in vitro approaches to identify therapeutic candidates among approved drugs that target the SARS-CoV-2 life cycle.
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Mechanism of SARS-CoV-2 polymerase inhibition by remdesivir
Goran Kokic,Hauke S. Hillen,Hauke S. Hillen,Dimitry Tegunov,Christian Dienemann,Florian Seitz,Jana Schmitzová,Lucas Farnung,Aaron Siewert,Claudia Hoebartner,Patrick Cramer +10 more
TL;DR: It is shown that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation, thereby stalling RdRp.
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