Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
Department of Internal Medicine, School of Medicine, Fasa University of Medical Science, Fasa, Iran.
Biomed Res Int. 2022 Jul 7;2022:7341493. doi: 10.1155/2022/7341493. eCollection 2022.
In this work, the discovery and description of PF-07321332, a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, and excellent selection of off-target and in vivo immune profiles are reported. Various drugs and novel compound candidates for the treatment of the COVID-19 pandemic have been developed. PF-07321332 (or nirmatrelvir) is a new oral antiviral drug developed by Pfizer. In response to the pandemic, Pfizer has developed the COVID vaccine and in 2022 will launch its new major anti-SARS-Cov-2 protease inhibitor (PI). The combination of ritonavir and nirmatrelvir is under study in phase III of the clinical trial with a brand name Paxlovid. Paxlovid is an active 3Cl protease inhibitor. Paxlovid exerts its antiviral efficacy by inhibiting a necessary protease in the viral replication procedure. Proteases of coronavirus cleave several sites in the viral polyprotein where pyrrolidone was replaced by flexible glutamine. Due to the coronavirus pandemic, there is high demand for synthesis and development of this novel drug. Herein, we report the synthetic route and the mechanism of action was recently published on nirmatrelvir. Also, a comparison of the performance of two new oral antiviruses (molnupiravir and nirmatrelvir) for the treatment of COVID-19 is described. This review will be helpful for different disciplines such as biochemistry, organic chemistry, medicinal chemistry, and pharmacology.
本文报道了 PF-07321332 的发现和描述,这是一种主要的可生物利用的口服 SARS-CoV-2 蛋白酶抑制剂,具有体外抗人类冠状病毒活性,以及出色的靶向和体内免疫特征选择。已经开发了各种用于治疗 COVID-19 大流行的药物和新型化合物候选药物。PF-07321332(或奈玛特韦)是辉瑞公司开发的一种新型口服抗病毒药物。针对大流行,辉瑞公司开发了 COVID 疫苗,并将于 2022 年推出其新型主要抗 SARS-CoV-2 蛋白酶抑制剂(PI)。利托那韦和奈玛特韦的组合正在进行 III 期临床试验,商品名为 Paxlovid。Paxlovid 是一种活性 3C 蛋白酶抑制剂。Paxlovid 通过抑制病毒复制过程中必需的蛋白酶来发挥其抗病毒功效。冠状病毒的蛋白酶在病毒多蛋白中几个位点处切割,其中吡咯烷酮被灵活的谷氨酰胺取代。由于冠状病毒大流行,对这种新型药物的合成和开发有很高的需求。在此,我们报告了奈玛特韦的合成路线和作用机制,该机制最近已在其出版物上发表。此外,还描述了两种新型口服抗病毒药物(莫努匹拉韦和奈玛特韦)治疗 COVID-19 的性能比较。本综述将有助于生物化学、有机化学、药物化学和药理学等不同学科。