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.
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.
Biophys Chem. 2021 Sep;276:106610. doi: 10.1016/j.bpc.2021.106610. Epub 2021 May 28.
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.
在新千年，新型冠状病毒已经爆发了三次：SARS-CoV、MERS-CoV 和 SARS-CoV-2。不幸的是，我们仍然没有针对这些病毒引起的疾病的药物。SARS-CoV-2 的大流行提醒我们，迫切需要寻找具有完全不同机制的新药，这些药物可能针对冠状病毒的特定弱点。在此，我们通过计算评估了二硫代氨基甲酸盐（disulfiram）的靶向氧化策略（TOS），以抑制 SARS-CoV-2，该药物是一种有 70 年历史的抗酗酒药物，并预测了一种多靶点机制。通过对 32143 个二硫键的虚拟筛选，提出了针对 SARS-CoV-2 两种巯基蛋白酶的有希望的 TOS 候选药物的初步清单。
