针对 SARS-CoV-2 冠状病毒主蛋白酶的潜在共价药物。
Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus.
机构信息
National '111' Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Industrial Fermentation (Ministry of Education).
Institute of Biomedical and Pharmaceutical Sciences, Hubei Key Laboratory of Industrial Microbiology, School of Food and Biological Engineering, Hubei University of Technology, Wuhan 430068, China.
出版信息
Bioinformatics. 2020 Jun 1;36(11):3295-3298. doi: 10.1093/bioinformatics/btaa224.
MOTIVATION
Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19.
RESULTS
Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19.
CONTACT
动机
自 2019 年 12 月以来，新发现的冠状病毒 SARS-CoV-2 在全球范围内引发了大规模的健康危机，迄今为止已导致超过 70000 例 COVID-19 感染。急需针对 SARS-CoV-2 的临床药物来降低确诊 COVID-19 患者的高死亡率。传统的从头药物发现需要 10 多年的时间，因此药物重定位似乎是目前寻找治疗 COVID-19 潜在药物的最佳选择。
结果
与传统的非共价药物相比，近年来，共价药物由于在精心设计、效率和患者负担方面具有潜在的特异性优势，引起了越来越多的关注。我们最近开发了一种名为 SCAR（空间冲突缓解受体）的计算方案，用于发现针对 SARS-CoV-2 主要蛋白酶（3CLpro）的共价药物。在这项工作中，我们使用 SCAR 方案来识别可能的共价药物（已批准或临床测试）针对 SARS-CoV-2 的主要蛋白酶（3CLpro）。我们确定了 11 个潜在的命中化合物，其中至少 6 个命中化合物是 SCAR 方案特有的。由于这些已识别药物的临床前或临床信息已经可用，它们可能已经准备好用于 COVID-19 的临床治疗测试。
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