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中国科学家解析瑞德西韦抑制新冠病毒的结构基础
作者:小柯机器人 发布时间:2020/5/2 13:24:01

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。

研究人员报告了SARS-CoV-2的RNA依赖性RNA聚合酶(RdRp)冷冻电镜结构,其以2.8Å的分辨率呈apo形式,或以2.5Å的分辨率与50个碱基的模板引物RNA和瑞德西韦形成复合体。
 
复合物结构表明,部分双链RNA模板插入了RdRp的中央通道,其中在第一个复制的碱基对处,瑞德西韦共价掺入引物链中,并终止了链的延长。这些结构为病毒RNA复制机制提供了重要见解,并为抗病毒感染药物设计提供了合理的模板。
 
附:英文原文

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

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037