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 strategy for evaluating potential antiviral resistance to small molecule drugs and application to SARS-CoV-2
TL;DR: In this paper , a generic strategy to evaluate which viral mutations might diminish drug efficacy and applied it to assess how SARS-CoV-2 evolution may affect the efficacy of current approved/candidate small-molecule antivirals for M pro , PL pro , and RdRp.
In silico screening of natural antivirals as potential inhibitors of SARS‐CoV‐2 virus
TL;DR: Sotetsuflavone is the most potent compound that inhibits four targets, with drug‐like properties, good intestinal absorption, and low toxicity, according to molecular docking and molecular dynamics simulations.
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Evaluating the Virology and Evolution of Seasonal Human Coronaviruses Associated with the Common Cold in the COVID-19 Era
Cameron Harrison,Jayden M. Doster,Emily H. Landwehr,Nidhi P. Kumar,Ethan J. White,Dia C. Beachboard,Christopher C. Stobart +6 more
TL;DR: In this article , the authors evaluate the virology, emergence, and evolution of four endemic coronaviruses associated with the common cold, their relationship to pandemic SARS-CoV-2, and discuss the potential for future emergent human coronavirus infections.
Posted ContentDOI
Structural Proteomics-Driven Targeted Design of Favipiravir-Binding Site in The RdRp of SARS-CoV-2 Unravels Susceptible Hotspots and Resistance Mutations
TL;DR: High-throughput interface-based protein design is used to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp and improve the understanding of the potential signatures of adaptation in SARS-CoV-2 against favipIRavir and management of COVID-19.
Book ChapterDOI
In silico analysis for such natural compounds and COVID-19
TL;DR: In this article , the effects of the mentioned natural metabolites repurposed for coronavirus diseases, especially for SARS-CoV-2, should be evaluated more by clinical investigation so that we may be able to develop potential drugs for most challenging respiratory diseases.
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