Critical Care Department, National Research Institute ofTuberculosis and Lung Disease, Shahid Beheshti University of Medical Science,Tehran, Iran; Chronic Respiratory Disease Research Center, National ResearchInstitute of Tuberculosis and Lung Disease, Shahid Beheshti University ofMedical Science, Tehran, Iran.
School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan Universityof Medical Sciences, Kashan, Iran.
Biomed Pharmacother. 2023 Jun;162:114367. doi: 10.1016/j.biopha.2023.114367. Epub 2023 Feb 6.
Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.
尽管需要针对 COVID-19 大流行的新型、有效治疗方法,但目前尚无治愈方案,因此患者只能依赖支持性和非特异性治疗方法。一些 SARS-CoV-2 蛋白,如 3 个结构域蛋白酶(3CLpro)或主要蛋白酶(Mpro),已被确定为有希望的抗病毒药物靶点。Mpro 在病毒的蛋白加工和发病机制中起着重要作用,可能是一个有用的治疗靶点。抗病毒药物奈玛特韦可通过抑制 Mpro 阻止 SARS-CoV-2 复制。奈玛特韦与另一种 HIV 蛋白酶抑制剂利托那韦联合使用,制成了帕罗韦德(奈玛特韦/利托那韦)。利托那韦抑制细胞色素 P450 3A 代谢酶,从而延长奈玛特韦的半衰期,因此利托那韦具有药理学增强作用。尽管 SARS-CoV-2 病毒基因组发生了重大改变,但奈玛特韦仍对当前的冠状病毒变体表现出强大的抗病毒活性。尽管如此,仍有几个悬而未决的问题。本文综述了奈玛特韦和利托那韦治疗 SARS-CoV-2 感染的疗效及其安全性和可能的副作用的最新文献。