【摘要】 由冠状病毒感染引发的全球性疫情对人类健康造成了巨大威胁,时至今日尚未有特效的治疗药物或疫苗问世,因此开发具有临床应用价值的抗冠状病毒药物刻不容缓. 3CL蛋白酶在冠状病毒的复制过程中起关键作用,其序列具有高度保守性,是进行抗冠状病毒药物设计的关键靶标.本文围绕SARS-CoV、MERS-CoV和SARS-CoV-2 3CL蛋白酶的结构与功能关系、已报道抑制剂的结构类型与活性及可能的作用机制进行归纳总结,探讨3CL蛋白酶抑制剂研发的新方向,为抗新型冠状病毒药物研发提供参考.更多还原

【Abstract】 Global pandemic caused by coronavirus remains a huge threat to public health. No efficacious drugs and vaccines are available so far. Therefore, it is urgent to design and develop anti-coronavirus clinical drugs. The 3C-like protease is a promising key drug target, as it plays a pivotal role in viral replication and is highly conserved in all coronaviruses. This review summarizes the major advances in the structure, catalytic mechanism, substrate specificity,auto-processing mechanism and inhibitor discovery for the 3C-like protease of SARS-CoV, MERS-CoV and SARS-CoV-2, classifies known inhibitors and analyzes their possible inhibition mechanisms. Potential future directions of 3C-like protease inhibitor discovery with novel mechanisms are also discussed.更多还原