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 Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses
Yucheng Zheng,Shiliang Li,Kun Song,Jiajie Ye,Wenkang Li,Yifan Zhong,Ziyan Feng,Simeng Liang,Zeng Cai,Ke Xu +9 more
TL;DR: The multiple functions of DHOD Hi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.
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Overcoming nonstructural protein 15-nidoviral uridylate-specific endoribonuclease (nsp15/NendoU) activity of SARS-CoV-2
TL;DR: A novel hypothetical approach is described: combining available broad-spectrum antiviral agents such as nucleoside analogs with potential inhibitors of NendoU, for example nsp15 RNA substrate mimetics, to constitute a ‘double-hit’ whereby two CoV-unique protein elements of the replicase–transcriptase complex are inhibited simultaneously.
Journal ArticleDOI
SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms
Jiaqi Li,Hui-min Jia,Miaomiao Tian,Nijin Wu,Xia Yang,Jianni Qi,Wanhua Ren,Feifei Li,Hongjun Bian +8 more
TL;DR: The principal purpose of the review is to update information on the COVID-19 outbreak, and performs an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms.
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Characterizing SARS-CoV-2 mutations in the United States
TL;DR: Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, Wang et al. as mentioned in this paper revealed that the US SARS-CoV-2 has four substrains and five of the top SARS CoV2 mutations were first detected in China, Singapore, and the United Kingdom (1 case).
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Agathis robusta Bark Essential Oil Effectiveness against COVID-19: Chemical Composition, In Silico and In Vitro Approaches
TL;DR: Using this EO or its individual components for the protection against or treatment of COVID-19 is suggested, with good binding affinities of the components to the active site of the selected targets, especially the RBD.
References
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