Ren Jiayi, Zhang Zhengfu, Xia Yi, Zhao Daqun, Li Dingqin, Zhang Shujun
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China.
Molecules. 2025 Jan 16;30(2):351. doi: 10.3390/molecules30020351.
The three-year COVID-19 pandemic 'has' caused a wide range of medical, social, political, and financial implications. Since the end of 2020, various mutations and variations in SARS-CoV-2 strains, along with the immune escape phenomenon, have emerged. There is an urgent need to identify a relatively stable target for the development of universal vaccines and drugs that can effectively combat both SARS-CoV-2 strains and their mutants. Currently, the main focus in treating SARS-CoV-2 lies in disrupting the virus's life cycle. The main protease (M) is closely associated with virus replication and maturation and plays a crucial role in the early stages of infection. Consequently, it has become an important target for the development of SARS-CoV-2-specific drugs. This review summarizes the recent research progress on the novel coronavirus's main proteases, including the pivotal role of M in the virus's life cycle, the structure and catalytic mechanism of M, the self-maturation mechanism of M, the role of M in virus immune escape, the current methods of developing antiviral drugs targeting M, and the key drugs that have successfully entered clinical trials. The aim is to provide researchers involved in the development of antiviral drugs targeting M with systematic and comprehensive information.
三年的新冠疫情“已经”引发了广泛的医学、社会、政治和金融影响。自2020年底以来,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)毒株出现了各种突变和变异,同时伴有免疫逃逸现象。迫切需要确定一个相对稳定的靶点,以开发能够有效对抗SARS-CoV-2毒株及其突变体的通用疫苗和药物。目前,治疗SARS-CoV-2的主要重点在于破坏病毒的生命周期。主要蛋白酶(M)与病毒复制和成熟密切相关,在感染早期起着关键作用。因此,它已成为开发SARS-CoV-2特异性药物的重要靶点。本综述总结了新型冠状病毒主要蛋白酶的最新研究进展,包括M在病毒生命周期中的关键作用、M的结构和催化机制、M的自我成熟机制、M在病毒免疫逃逸中的作用、目前开发靶向M的抗病毒药物的方法以及已成功进入临床试验的关键药物。目的是为参与开发靶向M的抗病毒药物的研究人员提供系统而全面的信息。