Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first…

• NN
  National Natural Science Foundation of China

  Awards: 31770796, 81922071
• NS
  National Science and Technology Major Project

  Award: 2018ZX09711002
• NK
  National Key Research and Development Program of China Stem Cell and Translational Research

  Award: 2016YFA050230