Rxivist logo

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation

By Xuelan Zhou, Fangling Zhong, Cheng Lin, Xiaohui Hu, Yan Zhang, Bing Xiong, Xiushan Yin, Jinheng Fu, Wei A He, Jingjing Duan, Yang Fu, Huan Zhou, Qisheng Wang, Jian Li, Jin Zhang

Posted 13 May 2020
bioRxiv DOI: 10.1101/2020.05.12.092171

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5). The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents. ### Competing Interest Statement The authors have declared no competing interest.

Download data

  • Downloaded 616 times
  • Download rankings, all-time:
    • Site-wide: 46,853
    • In biochemistry: 1,190
  • Year to date:
    • Site-wide: 54,505
  • Since beginning of last month:
    • Site-wide: 34,600

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News