首个口服非共价、非肽性严重急性呼吸综合征冠状病毒23CL蛋白酶抑制剂——Ensitrelvir

First oral non-covalent,non-peptide severe acute respiratory syndrome coronavirus 23CL protease inhibitor:Ensitrelvir

北海道大学和盐野义制药公司基于结构的药物设计策略联合研发了第一个口服非共价、非肽性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)3CL蛋白酶抑制剂Ensitrelvir。Ensitrelvir对SARS-CoV-2各变异株均表现出抗病毒活性,并在体内显示出良好的药物代谢动力学特性。2022年4月盐野义制药公司公布Ensitrelvir临床Ⅱ/Ⅲ期试验中Ⅱb期部分结果,其能够快速清除传染性SARS-CoV-2,在治疗的第4天,病毒滴度阳性的患者比例比安慰剂组减少了约90%;同时试验中未观察到严重不良反应。Ensitrelvir有望摆脱对细胞色素P450酶抑制剂(如利托那韦)的依赖,实现单药治疗新型冠状病毒肺炎(新冠肺炎),满足正在服用慢性病药物的高风险新冠肺炎患者治疗需求。本文对Ensitrelvir的基本信息、作用机制、临床前研究、临床研究等作一综述。

Ensitrelvir is the first oral non-covalent,non-peptide severe acute respiratory syndrome coronavirus 2(SARSCo V-2)3CL protease inhibitor,that was discovered through joint research by Hokkaido University and Shionogi&Co.,Ltd.(Shionogi).Ensitrelvir exhibited antiviral activity against all variants of SARS-Co V-2 and showed promising pharmacokinetic properties in vivo.In April 2022,Shionogi announced the partial results of phaseⅡb in the phaseⅡ/Ⅲclinical trial of Ensitrelvir,showing that Ensitrelvir could rapidly clear the infectious SARS-Co V-2.On the fourth day of treatment,the proportion of patients with positive viral titers was reduced by approximately 90%in the Ensitrelvir group compared with the placebo group.Meanwhile,no serious adverse reactions were observed in the trial.Ensitrelvir is expected to be in dependent of cytochrome P450 inhibitors(such as Ritonavir),realize the single-agent treatment of coronavirus disease 2019(COVID-19),and meet the treatment needs of high-risk COVID-19 patients concomitant with drugs for chronic diseases.This article reviews the basic information,mechanism of action,preclinical research,and clinical progress of Ensitrelvir.