Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2
Potential clinical drugs as covalent inhibitors of the priming proteases of the spike protein of SARS-CoV-2
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作为 SARS-CoV-2 刺突蛋白引发蛋白酶共价抑制剂的潜在临床药物
DOI：
10.1016/j.csbj.2020.08.016
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发表时间：
2020-01-01
影响因子：
6
通讯作者：
Liu, Sen
中科院分区：
文献类型：
--
作者：
Li, Qizhang;Wang, Zhiying;Liu, Sen
在不到8个月的时间里，由SARS-CoV-2(严重急性呼吸综合征冠状病毒2号)病毒引发的新冠肺炎(2019年冠状病毒病)已导致全球2000多万确诊病例和70多万人死亡。随着这种疾病在全球范围内的日益蔓延，缺乏有效的治疗SARS-CoV-2感染的药物使情况变得更加危险和不可预测。尽管许多力量正在加快开发预防和治疗疗法，但在几个月内不太可能有任何从头开始的药物。药物再利用有望大大节省药物开发的时间，因为它可以利用现有的临床药物来治疗新的疾病。基于本实验室最近开发的空间冲突缓解受体(SCAR)策略，我们对临床和研究药物库进行了筛选，确定了9种可能作为SARS-CoV-2刺突蛋白启动蛋白的共价抑制剂的药物(组织蛋白酶B、组织蛋白酶L和TMPRSS2)。在这些药物中，五种是已知的共价抑制剂，一种是抗病毒药物。因此，我们希望我们的工作能为抗SARS-CoV-2药物的开发提供合理和及时的帮助。(C)2020年提交人(S)。由Elsevier B.V.代表计算和结构生物技术研究网络出版。
In less than eight months, the COVID-19 (coronavirus disease 2019) caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus has resulted in over 20,000,000 confirmed cases and over 700,000 deaths around the world. With the increasing worldwide spreading of this disease, the lack of effective drugs against SARS-CoV-2 infection makes the situation even more dangerous and unpredictable. Although many forces are speeding up to develop prevention and treatment therapeutics, it is unlikely that any de novo drugs will be available in months. Drug repurposing holds the promise to significantly save the time for drug development, since it could use existing clinic drugs to treat new diseases. Based on the "steric-clashes alleviating receptor (SCAR)" strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2. Among these hits, five are known covalent inhibitors, and one is an anti-virus drug. Therefore, we hope our work would provide rational and timely help for developing anti-SARS-CoV-2 drugs. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.