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

  1. Wanchao Yin
  2. Chunyou Mao
  3. Xiaodong Luan
  4. Dan-Dan Shen
  5. Qingya Shen
  6. Haixia Su
  7. Xiaoxi Wang
  8. Fulai Zhou
  9. Wenfeng Zhao
  10. Minqi Gao
  11. Shenghai Chang
  12. Yuan-Chao Xie
  13. Guanghui Tian
  14. He-Wei Jiang
  15. Sheng-Ce Tao
  16. Jingshan Shen
  17. Yi Jiang
  18. Hualiang Jiang
  19. Yechun Xu
  20. Shuyang Zhang
  21. Yan Zhang
  22. H. Eric Xu
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Abstract

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.

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