A computational evaluation of targeted oxidation strategy (TOS) for potential inhibition of SARS-CoV-2 by disulfiram and analogues.

Xu, Luyan; Tong, Jiahui; Wu, Yiran; Zhao, Suwen; Lin, Bo-Lin

Xu, Luyan; Tong, Jiahui; Wu, Yiran; Zhao, Suwen; Lin, Bo-Lin.

Xu L; School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China; University of Chinese A
Tong J; iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chines
Wu Y; iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
Zhao S; iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: zhaosw@shanghaitech.edu.cn.
Lin BL; School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China; University of Chinese A

Biophys Chem ; 276: 106610, 2021 09.

Article in English | MEDLINE | ID: covidwho-1252522

ABSTRACT

ABSTRACT

In the new millennium, the outbreak of new coronavirus has happened three times SARS-CoV, MERS-CoV, and SARS-CoV-2. Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses. The pandemic of SARS-CoV-2 reminds us the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses. Herein, we disclose a computational evaluation of targeted oxidation strategy (TOS) for potential inhibition of SARS-CoV-2 by disulfiram, a 70-year-old anti-alcoholism drug, and predict a multiple-target mechanism. A preliminary list of promising TOS drug candidates targeting the two thiol proteases of SARS-CoV-2 are proposed upon virtual screening of 32,143 disulfides.

Subject(s)

Alcohol Deterrents/chemistry; Antiviral Agents/chemistry; Coronavirus 3C Proteases/antagonists & inhibitors; Coronavirus Papain-Like Proteases/antagonists & inhibitors; Disulfiram/chemistry; Protease Inhibitors/chemistry; SARS-CoV-2/chemistry; Alcohol Deterrents/pharmacology; Antiviral Agents/pharmacology; Catalytic Domain; Coronavirus 3C Proteases/chemistry; Coronavirus 3C Proteases/genetics; Coronavirus 3C Proteases/metabolism; Coronavirus Papain-Like Proteases/chemistry; Coronavirus Papain-Like Proteases/genetics; Coronavirus Papain-Like Proteases/metabolism; Disulfiram/pharmacology; Drug Repositioning; Gene Expression; Humans; Kinetics; Molecular Docking Simulation; Oxidation-Reduction; Protease Inhibitors/pharmacology; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Quantum Theory; SARS-CoV-2/enzymology; Substrate Specificity; Thermodynamics; COVID-19 Drug Treatment

Keywords

COVID-19; Coronavirus; Disulfide; SARS-CoV-2; Target oxidation strategy; Thiol protease

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Protease Inhibitors / Disulfiram / Alcohol Deterrents / Coronavirus 3C Proteases / Coronavirus Papain-Like Proteases / SARS-CoV-2 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: Biophys Chem Year: 2021 Document Type: Article

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