Science. Structure of the RNA-dependent RNA polymerase from COVID-19 virus

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Science. 2020 Apr 10. pii: eabb7498. doi: 10.1126/science.abb7498. [Epub ahead of print]
Structure of the RNA-dependent RNA polymerase from COVID-19 virus.


Gao Y^#1,2, Yan L^#1, Huang Y^#1, Liu F^#2, Zhao Y², Cao L³, Wang T¹, Sun Q², Ming Z⁴, Zhang L¹, Ge J¹, Zheng L¹, Zhang Y¹, Wang H^2,5, Zhu Y², Zhu C², Hu T², Hua T², Zhang B², Yang X², Li J², Yang H², Liu Z², Xu W², Guddat LW⁶, Wang Q⁷, Lou Z⁸, Rao Z^8,2,3,9.

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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-? 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.
Copyright ? 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.



PMID:32277040DOI:10.1126/science.abb7498