近日,中国科学院上海药物研究所徐华强研究员、浙江大学张岩教授、北京协和医院张抒扬教授和上海药物研究所许叶春研究员等研究人员,合作报道了瑞德西韦抑制SARS-CoV-2 RNA依赖性RNA聚合酶的结构基础。2020年5月1日,相关论文在线发表于《科学》杂志。
Title: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
Author: Wanchao Yin, Chunyou Mao, Xiaodong Luan, Dan-Dan Shen, Qingya Shen, Haixia Su, Xiaoxi Wang, Fulai Zhou, Wenfeng Zhao, Minqi Gao, Shenghai Chang, Yuan-Chao Xie, Guanghui Tian, He-Wei Jiang, Sheng-Ce Tao, Jingshan Shen, Yi Jiang, Hualiang Jiang, Yechun Xu, Shuyang Zhang, Yan Zhang, H. Eric Xu
Issue&Volume: 2020/05/01
Abstract: 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 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 resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 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.
DOI: 10.1126/science.abc1560
Source: https://science.sciencemag.org/content/early/2020/04/30/science.abc1560