McCarthy Matthew W
Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Expert Opin Pharmacother. 2022 Dec;23(18):1995-1998. doi: 10.1080/14656566.2022.2146493. Epub 2022 Nov 10.
First-generation therapeutics have improved clinical outcomes in patients infected with SARS-CoV-2. However, viral evolution has produced variants and subvariants capable of resisting many of these drugs and novel treatment strategies are urgently needed.
A corporate compound library screen identified ensitrelvir (formerly S-217622), a non-covalent, non-peptidic, orally bioavailable small-molecule protease inhibitor as a potential treatment for SARS-CoV-2. Ensitrelvir cleaves the active site of the 3C-like protease (3CL), which is conserved across SARS-CoV-2 variants and subvariants, with no human cell protease with similar specificity.
Ensitrelvir demonstrates strong antiviral activity against the SARS-CoV-2 Omicron subvariants BA.4 and BA.5, which have driven new waves of infection throughout 2022, suggesting a potential therapeutic option for patients with COVID-19. This manuscript reviews what is known about ensitrelvir and explores how this drug may be used in the future to address the SARS-CoV-2 pandemic.
第一代治疗方法已改善了感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）患者的临床结局。然而，病毒进化产生了能够抵抗许多此类药物的变体和亚变体，因此迫切需要新的治疗策略。
一项企业化合物库筛选确定了恩昔瑞韦（以前称为S-217622），一种非共价、非肽类、口服生物可利用的小分子蛋白酶抑制剂，作为SARS-CoV-2的潜在治疗方法。恩昔瑞韦切割3C样蛋白酶（3CL）的活性位点，该位点在SARS-CoV-2变体和亚变体中保守，且没有具有类似特异性的人类细胞蛋白酶。
恩昔瑞韦对SARS-CoV-2奥密克戎亚变体BA.4和BA.5表现出强大的抗病毒活性，这两种亚变体在2022年引发了新一波感染浪潮，这表明它可能是新冠肺炎患者的一种潜在治疗选择。本文综述了关于恩昔瑞韦的已知信息，并探讨了该药物未来如何用于应对SARS-CoV-2大流行。
