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

American Association for the Advancement of Science (AAAS) - Tập 368 Số 6498 - Trang 1499-1504 - 2020
Wanchao Yin1,2, Chunyou Mao1, Xiaodong Luan3,4,5, Dan‐Dan Shen1, Qingya Shen1, Haixia Su2,6, Xiaoxi Wang2, Fulai Zhou2, Wenfeng Zhao2, Minqi Gao7, Shenghai Chang8,9, Yuanchao Xie2, Guanghui Tian2, He‐wei Jiang10, Sheng‐ce Tao10, Jingshan Shen2,6, Yi Jiang2,6, Hualiang Jiang2,6, Yechun Xu2,6, Shuyang Zhang3,4,5, Yan Zhang1,11, H. Eric Xu2,6
1Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
2The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
3Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
4School of Medicine, Tsinghua University, Haidian District, Beijing 100084, China.
5Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
6University of Chinese Academy of Sciences, Beijing, 100049, China
7WuxiBiortus Biosciences Co. Ltd., Jiangyin 214437, China.
8Center of Cryo-Electron Microscopy, Zhejiang University School of Medicine, Hangzhou 310058, China.
9Center of Diagnostic Electron Microscopy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
10Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China
11Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou 310058, China

Tóm tắt

A wrench in the works of COVID-19 Understanding the inner workings of the virus that causes coronavirus disease 2019 (COVID-19) may help us to disrupt it. Yin et al. focused on the viral polymerase essential for replicating viral RNA. They determined a structure of the polymerase bound to RNA and to the drug remdesivir. Remdesivir mimics an RNA nucleotide building block and is covalently linked to the replicating RNA, which blocks further synthesis of RNA. The structure provides a template for designing improved therapeutics against the viral polymerase. Science , this issue p. 1499

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