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

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

doi:10.1016/j.bpc.2021.106610

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

Biophys Chem. 2021 Sep:276:106610. doi: 10.1016/j.bpc.2021.106610. Epub 2021 May 28.

Authors

Luyan Xu¹, Jiahui Tong², Yiran Wu³, Suwen Zhao⁴, Bo-Lin Lin⁵

Affiliations

¹ 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 Academy of Sciences, Beijing 100049, China.
² 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, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
⁴ iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: zhaosw@shanghaitech.edu.cn.
⁵ 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 Academy of Sciences, Beijing 100049, China. Electronic address: linbl@shanghaitech.edu.cn.

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Alcohol Deterrents
Antiviral Agents
Protease Inhibitors
Coronavirus Papain-Like Proteases
papain-like protease, SARS-CoV-2
Coronavirus 3C Proteases
Disulfiram