临床阶段及已批准上市新型冠状病毒3CL蛋白酶抑制剂的研究进展

Recent progress on clinic and marketed 3C like protease inhibitors of SARS⁃CoV⁃2

2019年出现的新型冠状病毒(SARS-CoV-2)导致了一场席卷全球的大流行疾病,截止2022年底,全球新冠感染病例超过6.7亿,死亡病例已经超过700万,对社会和经济造成了巨大损失。尽管在前期的临床研发过程中,疫苗技术率先用于临床并实现全球范围内的接种,为预防病毒提供了免疫屏障;但新型冠状病毒变异能力强,亟需针对潜在的病毒变异开发更加有效的治疗药物。SARS-CoV-2的3CL蛋白酶(3CLpro),因其在病毒生命周期中的重要性及其在不同冠状病毒中的高度保守性,已成为临床药物开发极具吸引力的靶点。截止2023年初,以3CLpro为靶点的抑制剂已有多个进入临床阶段或已批准上市。本文主要针对已经进入临床阶段和已经上市的新型冠状病毒3CLpro抑制剂进行分类总结,为未来针对冠状病毒抑制剂的研发和降低疫情风险提供一定的理论借鉴。

The emergence of the severe acute respiratory syndrome coronavirus⁃2(SARS⁃CoV⁃2)in 2019 has led to a prolonged global epidemic.By the end of 2022,the COVID⁃19 has cause more than 670 million infection,7 million deaths,and has induced huge social and economic losses.Although the vaccine technology has been widely applied in clinic trial,providing a valuable barrier against the COVID⁃19 virus,while the strong mutation ability of this virus makes the urgency for the development of more effective anti⁃infection methods.The 3C like protease(3CL pro),due to its importance in the viral life and high conservation among different coronaviruses,has become an attractive target protein for the development of inhibitors.Until early 2023,several drugs with high inhibitory activity against 3CL pro have been developed and entered the clinical stage or approved on the market.This paper is to classify and summarize the 3CL pro inhibitors that have been in different stages of the clinic or approved on the market,so as to provide some theoretical references for the future research and development of coronavirus inhibitors and the reduction of epidemic risk.