新型冠状病毒SARS-CoV-2 M^(pro)靶向抑制剂研究进展

Recent advances of inhibitors targeting main protease of SARS-CoV-2

冠状病毒(coronaviruses,CoVs)是单链正义包膜RNA病毒。严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是已知感染人类的第七种冠状病毒,并于2019年12月引发了新的冠状病毒病(COVID-19)。COVID-19具有高度传染性,自发现以来迅速在全球范围传播。随着SARS-CoV-2的全基因组和系统发育被解析,以及SARS-CoV-2晶体结构的确定,针对COVID-19的靶向抑制剂和疫苗正在迅速研发中。主要蛋白酶M^(pro)是SARS-CoV-2复制的关键酶,由多肽编码,负责将多肽加工成功能蛋白。目前,对SARS-CoV-2还没有有效的治疗方法。本文重点关注自2019年底SARS-CoV-2爆发以来发现的各种有效的以M^(pro)为靶标的抗SARS-CoV-2化学疗法的现状,汇总了拟肽类、非拟肽类的小分子抑制剂、金属络合物类等M^(pro)抑制剂,并重点介绍了这些抑制剂的结构特点和结合方式。

Coronaviruses(CoVs) are single-stranded positive-sense enveloped RNA viruses.Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),which is the seventh coronavirus known to infect humans, causes a new coronavirus disease(COVID-19) outbreak since December 2019.The Main protease(M^(pro)) is a key enzyme for SARS-CoV-2 replication, which is encoded by the polypeptide and responsible for processing the polypeptide into functional proteins.This review focused on the status of various effective anti-SARS-CoV-2 chemotherapies targeting M^(pro) discovered since the outbreak of SARS-CoV-2 in the end of 2019.The peptidomimetic, non-peptidomimetic small molecule inhibitors, metal coupling(complexation) inhibitors of SARS-CoV-2 were summarised, and the structural features and binding modes of these inhibitors were described in details.