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

Yin, Wanchao; Mao, Chunyou; Luan, Xiaodong; Shen, Dan-Dan; Shen, Qingya; Su, Haixia; Wang, Xiaoxi; Zhou, Fulai; Zhao, Wenfeng; Gao, Minqi; Chang, Shenghai; Xie, Yuan-Chao; Tian, Guanghui; Jiang, He-Wei; Tao, Sheng-Ce; Shen, Jingshan; Jiang, Yi; Jiang, Hualiang; Xu, Yechun; Zhang, Shuyang; Zhang, Yan; Xu, H. Eric

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 target of the antiviral drug, Remdesivir. Here we report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Ã… resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 Ã… 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 replicated base pair and terminates chain elongation. Our structures provide critical insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.