ABSTRACT
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.
Subject(s)
COVID-19 Drug Treatment , Pandemics , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 Vaccines , Coronavirus 3C Proteases , Cysteine Endopeptidases , Drug Combinations , Humans , Lactams , Leucine , Nitriles , Proline , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , Ritonavir , SARS-CoV-2 , Viral Nonstructural Proteins/chemistryABSTRACT
During the COVID-19 pandemic, various drug candidates have been developed, molnupiravir (MK-4482 and EIDD-2801), which is a new orally anti-viral agent under development for the treatment of COVID-19, is under study in the final stage of the clinical trial. Molnupiravir enhances the replication of viral RNA mutations in animals and humans. Due to the high demand for the synthesis of this drug, it was essential to develop an efficient and suitable synthetic pathway from raw material. In this study, molecular docking analysis on molnupiravir is examined also, the mechanism of action (MOA) and the recent synthetic pathway is reported. This review will be helpful to different disciplines such as medicinal chemistry, organic chemistry, biochemistry, and pharmacology.
ABSTRACT
During the COVID-19 pandemic, various drug candidates have been developed, molnupiravir (MK-4482 and EIDD-2801), which is a new orally anti-viral agent under development for the treatment of COVID-19, is under study in the final stage of the clinical trial. Molnupiravir enhances the replication of viral RNA mutations in animals and humans. Due to the high demand for the synthesis of this drug, it was essential to develop an efficient and suitable synthetic pathway from raw material. In this study, molecular docking analysis on molnupiravir is examined also, the mechanism of action (MOA) and the recent synthetic pathway is reported. This review will be helpful to different disciplines such as medicinal chemistry, organic chemistry, biochemistry, and pharmacology.