拟肽类冠状病毒主蛋白酶抑制剂的研究进展

Advances in peptidomimetic inhibitors of coronavirus main protease

冠状病毒(coronavirus,CoVs)是一类广泛存在、可感染人畜并引起严重急慢性呼吸道系统疾病的病原体。其中危害较为严重的是2003年暴发的SARS-CoV、2012年发现并广泛传播的MERS-CoV和2019年底暴发并持续至今的SARS-CoV-2,这些都属于β冠状病毒属。以冠状病毒主蛋白酶(M^(pro),3CL^(pro))为靶点的拟肽类抑制剂因其具有广谱和抗病毒效力强等优点而备受关注。本文针对拟肽类冠状病毒主蛋白酶抑制剂进行综述,根据设计策略中“warheads”(弹头)的不同进行分类,对抑制剂的分子结构、活性及其设计思路进行分析和总结,对冠状病毒抑制剂的进一步设计与开发具有重要的参考价值。

Coronavirus(CoVs)is a widespread pathogen that can infect humans and animals to cause serious acute and chronic respiratory diseases.Among them,SARS-CoV broke out in 2003,MERS-CoV was discovered and spread widely in 2012,and SARS-CoV-2 emerged at the end of 2019.They all belong toβ-coronavirus.Peptidomimetic inhibitors targeting coronavirus main proteases(M^(pro),3CL^(pro))have attracted much attention because of their broad spectrum and strong antiviral efficacy.In this review,peptidomimetic inhibitors of coronavirus main protease were classified and summarized according to the different"warheads"in design strategy.And also,the molecular structures,biological activity and design ideas of the inhibitors were analyzed and discussed,which is aimed to provide useful reference for further design and development of coronavirus inhibitors.