Cui Wen, Yang Kailin, Yang Haitao
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
School of Life Science and Technology, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
Front Mol Biosci. 2020 Dec 4;7:616341. doi: 10.3389/fmolb.2020.616341. eCollection 2020.
The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) rapidly turned into an unprecedented pandemic of coronavirus disease 2019 (COVID-19). This global healthcare emergency marked the third occurrence of a deadly coronavirus (CoV) into the human society after entering the new millennium, which overwhelmed the worldwide healthcare system and affected the global economy. However, therapeutic options for COVID-19 are still very limited. Developing drugs targeting vital proteins in viral life cycle is a feasible approach to overcome this dilemma. Main protease (M) plays a dominant role in processing CoV-encoded polyproteins which mediate the assembly of replication-transcription machinery and is thus recognized as an ideal antiviral target. Here we summarize the recent progress in the discovery of anti-SARS-CoV-2 agents against M. Combining structural study, virtual screen, and experimental screen, numerous therapeutic candidates including repurposed drugs and designed compounds have been proposed. Such collaborative effort from the scientific community would accelerate the pace of developing efficacious treatment for COVID-19.
2019新型冠状病毒（2019-nCoV，后命名为严重急性呼吸综合征冠状病毒2）的突然爆发迅速演变成了一场前所未有的2019冠状病毒病（COVID-19）大流行。这一全球卫生紧急事件标志着进入新千年后致命冠状病毒第三次侵袭人类社会，它使全球医疗系统不堪重负，并影响了全球经济。然而，COVID-19的治疗选择仍然非常有限。开发针对病毒生命周期中关键蛋白的药物是克服这一困境的可行方法。主要蛋白酶（M）在处理冠状病毒编码的多聚蛋白中起主导作用，这些多聚蛋白介导复制转录机器的组装，因此被认为是理想的抗病毒靶点。在此，我们总结了针对M的抗SARS-CoV-2药物发现的最新进展。结合结构研究、虚拟筛选和实验筛选，已提出了许多治疗候选药物，包括重新利用的药物和设计的化合物。科学界的这种合作努力将加快开发COVID-19有效治疗方法的步伐。
