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

Liu, Pei; Liu, Hongbo; Sun, Qi; Liang, Hao; Li, Chunmei; Deng, Xiaobing; Liu, Ying; Lai, Luhua

Liu, Pei; Liu, Hongbo; Sun, Qi; Liang, Hao; Li, Chunmei; Deng, Xiaobing; Liu, Ying; Lai, Luhua.

Liu P; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Liu H; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Sun Q; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Liang H; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Li C; Center for Quantitative Biology, Peking University, Beijing, 100871, China.
Deng X; BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Liu Y; 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: liuying@pku.edu.cn.
Lai L; 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

Eur J Med Chem ; 206: 112702, 2020 Nov 15.

Article in English | MEDLINE | ID: covidwho-724946

ABSTRACT

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.

Subject(s)

Antiviral Agents/therapeutic use; Betacoronavirus/drug effects; Isatin/therapeutic use; Protease Inhibitors/therapeutic use; Viral Nonstructural Proteins/antagonists & inhibitors; Antiviral Agents/pharmacology; Coronavirus 3C Proteases; Cysteine Endopeptidases; Humans; Isatin/analogs & derivatives; Isatin/chemical synthesis; Models, Molecular; Molecular Docking Simulation; Protease Inhibitors/chemical synthesis; Protease Inhibitors/pharmacology; SARS-CoV-2; Structure-Activity Relationship

Keywords

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

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Viral Nonstructural Proteins / Betacoronavirus / Isatin Limits: Humans Language: English Journal: Eur J Med Chem Year: 2020 Document Type: Article Affiliation country: J.ejmech.2020.112702

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