tetano
Editor, Senior Moderator
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[SUP]#[/SUP][SUP]1,[/SUP][SUP]2[/SUP], Yan L[SUP]#[/SUP][SUP]1[/SUP], Huang Y[SUP]#[/SUP][SUP]1[/SUP], Liu F[SUP]#[/SUP][SUP]2[/SUP], Zhao Y[SUP]2[/SUP], Cao L[SUP]3[/SUP], Wang T[SUP]1[/SUP], Sun Q[SUP]2[/SUP], Ming Z[SUP]4[/SUP], Zhang L[SUP]1[/SUP], Ge J[SUP]1[/SUP], Zheng L[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wang H[SUP]2,[/SUP][SUP]5[/SUP], Zhu Y[SUP]2[/SUP], Zhu C[SUP]2[/SUP], Hu T[SUP]2[/SUP], Hua T[SUP]2[/SUP], Zhang B[SUP]2[/SUP], Yang X[SUP]2[/SUP], Li J[SUP]2[/SUP], Yang H[SUP]2[/SUP], Liu Z[SUP]2[/SUP], Xu W[SUP]2[/SUP], Guddat LW[SUP]6[/SUP], Wang Q[SUP]7[/SUP], Lou Z[SUP]8[/SUP], Rao Z[SUP]8,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]9[/SUP].
Author information
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
Structure of the RNA-dependent RNA polymerase from COVID-19 virus.
Gao Y[SUP]#[/SUP][SUP]1,[/SUP][SUP]2[/SUP], Yan L[SUP]#[/SUP][SUP]1[/SUP], Huang Y[SUP]#[/SUP][SUP]1[/SUP], Liu F[SUP]#[/SUP][SUP]2[/SUP], Zhao Y[SUP]2[/SUP], Cao L[SUP]3[/SUP], Wang T[SUP]1[/SUP], Sun Q[SUP]2[/SUP], Ming Z[SUP]4[/SUP], Zhang L[SUP]1[/SUP], Ge J[SUP]1[/SUP], Zheng L[SUP]1[/SUP], Zhang Y[SUP]1[/SUP], Wang H[SUP]2,[/SUP][SUP]5[/SUP], Zhu Y[SUP]2[/SUP], Zhu C[SUP]2[/SUP], Hu T[SUP]2[/SUP], Hua T[SUP]2[/SUP], Zhang B[SUP]2[/SUP], Yang X[SUP]2[/SUP], Li J[SUP]2[/SUP], Yang H[SUP]2[/SUP], Liu Z[SUP]2[/SUP], Xu W[SUP]2[/SUP], Guddat LW[SUP]6[/SUP], Wang Q[SUP]7[/SUP], Lou Z[SUP]8[/SUP], Rao Z[SUP]8,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]9[/SUP].
Author information
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