Nature Communications (Jun 2021)
Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease
- Haixia Su,
- Sheng Yao,
- Wenfeng Zhao,
- Yumin Zhang,
- Jia Liu,
- Qiang Shao,
- Qingxing Wang,
- Minjun Li,
- Hang Xie,
- Weijuan Shang,
- Changqiang Ke,
- Lu Feng,
- Xiangrui Jiang,
- Jingshan Shen,
- Gengfu Xiao,
- Hualiang Jiang,
- Leike Zhang,
- Yang Ye,
- Yechun Xu
Affiliations
- Haixia Su
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Sheng Yao
- University of Chinese Academy of Sciences
- Wenfeng Zhao
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Yumin Zhang
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
- Jia Liu
- University of Chinese Academy of Sciences
- Qiang Shao
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Qingxing Wang
- University of Chinese Academy of Sciences
- Minjun Li
- Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences
- Hang Xie
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Weijuan Shang
- State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
- Changqiang Ke
- State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Lu Feng
- State Key Laboratory of Drug Research, and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Xiangrui Jiang
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Jingshan Shen
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Gengfu Xiao
- University of Chinese Academy of Sciences
- Hualiang Jiang
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Leike Zhang
- University of Chinese Academy of Sciences
- Yang Ye
- University of Chinese Academy of Sciences
- Yechun Xu
- CAS Key Laboratory of Receptor Research, and Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- DOI
- https://doi.org/10.1038/s41467-021-23751-3
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 12
Abstract
SARS-CoV-2 3CL protease (3CLpro) is essential for coronavirus replication and of great interest as an antiviral drug target. Here, the authors show that the naturally occurring flavonoid myricetin is a non-peptidomimetic and covalent inhibitor of 3CLpro, and they solve crystal structures of 3CLpro with myricetin and derivatives, which reveal that the pyrogallol group covalently modifies the catalytic cysteine.
