Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors
Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors
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DOI：
10.1016/j.ijantimicag.2020.106055
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发表时间：
2020-08-01
影响因子：
10.8
通讯作者：
Ye, Wencai
中科院分区：
文献类型：
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作者：
He, Jun;Hu, Lijun;Ye, Wencai
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）与同属冠状病毒属的SARS-CoV和中东呼吸综合征冠状病毒（MERS-CoV）相似，可诱发严重急性呼吸系统疾病，对人类健康构成威胁。自引发2019冠状病毒病（COVID-19）的SARS-CoV-2感染爆发以来，该疾病已在全球迅速蔓延。因此，寻找能够抑制SARS-CoV-2的有效药物已成为全球的追求。3c样蛋白酶（3CL(pro)）水解病毒多蛋白产生功能蛋白，对冠状病毒复制至关重要，被认为是包括COVID-19在内的冠状病毒引起的疾病的重要治疗靶点。许多3CL（pro）抑制剂已被提出，一些新的候选药物已在临床前研究中取得成功。在这篇综述中，我们简要介绍了在确定3CL（pro）结构及其在冠状病毒复制中的功能方面的最新进展，并总结了3CL（pro）抑制剂及其作用机制的新见解。并讨论了3CL（pro）抑制剂在COVID-19治疗中的临床应用前景和局限性。(C) 2020 Elsevier B.V.和国际化学疗法学会。版权所有。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same Betacoronavirus genus, induces severe acute respiratory disease that is a threat to human health. Since the outbreak of infection by SARS-CoV-2 began, which causes coronavirus disease 2019 (COVID-19), the disease has rapidly spread worldwide. Thus, a search for effective drugs able to inhibit SARS-CoV-2 has become a global pursuit. The 3C-like protease (3CL(pro)), which hydrolyses viral polyproteins to produce functional proteins, is essential for coronavirus replication and is considered an important therapeutic target for diseases caused by coronaviruses, including COVID-19. Many 3CL(pro) inhibitors have been proposed and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe recent developments in determining the structure of 3CL(pro) and its function in coronavirus replication and summarise new insights into 3CL(pro) inhibitors and their mechanisms of action. The clinical application prospects and limitations of 3CL(pro) inhibitors for COVID-19 treatment are also discussed. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.