Potent inhibitors of SARS-CoV-2 3C-like protease derived from N-substituted isatin compounds

  • Eur J Med Chem. 2020 Nov 15;206:112702. doi: 10.1016/j.ejmech.2020.112702.
Pei Liu  1 ,  Hongbo Liu  1 ,  Qi Sun  1 ,  Hao Liang  1 ,  Chunmei Li  2 ,  Xiaobing Deng  1 ,  Ying Liu  3 ,  Luhua Lai  4
Affiliations
  • 1. BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
  • 2. Center for Quantitative Biology, Peking University, Beijing, 100871, China.
  • 3. BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China; Center for Quantitative Biology, Peking University, Beijing, 100871, China. Electronic address: [email protected].
  • 4. BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China; Center for Quantitative Biology, Peking University, Beijing, 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. Electronic address: [email protected].
PMID: 32798789 DOI: 10.1016/j.ejmech.2020.112702
Abstract

SARS-CoV-2 3C-like Protease is the main protease of SARS-CoV-2 and has been considered as one of the key targets for drug discovery against COVID-19. We identified several N-substituted isatin compounds as potent SARS-CoV-2 3C-like Protease inhibitors. The three most potent compounds inhibit SARS-CoV-2 3C-like Protease with IC50's of 45 nM, 47 nM and 53 nM, respectively. Our study indicates that N-substituted isatin compounds have the potential to be developed as broad-spectrum anti-coronavirus drugs.

Keywords
COVID-19; In vitro assay; N-substituted isatin compounds; SARS-CoV-2 3C-like protease; Structure-activity relationship.
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