Structural Basis for the Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir

By W. Yin, C. Mao, X. Luan, D. Shen, Q. Shen, H. Su, Xiao-xi Wang, F. Zhou, Wenfeng Zhao, M. Gao and 12 more. bioRxiv, 2020

784 citations recorded by the source corpus.

The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a direct target of the antiviral drug, Remdesivir. Here we report the structure of the SARS-CoV-2 RdRp either in the apo form or in complex with a 50-base template-primer RNA and Remdesivir at a resolution range of 2.5-2.8 Å. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is incorporated into the first replicated base pair and terminates the chain elongation. Our structures provide critical insights into the working mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.

Subfields: Cardiology and Cardiovascular Medicine, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/26afe30e374304de897a206b05f86e5c0e729b09

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In Cardiology and Cardiovascular Medicine

D. Bautista

Citations in the corpus

Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase (2020, background): “However, the existing structures of the complexes to date (Gao et al., 2020; Yin et al., 2020) have not revealed the complete nsp8.”
Structure of replicating SARS-CoV-2 polymerase (2020, background): “When our study was about to be completed, a manuscript became available that also describes a structure of a SARS-CoV-2 RdRp-RNA complex 24 .”
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs (2020, background): “72 e- Å2 in the first set (1-2007) and second set (2008-6309) of movies respectively.”