Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

• Published in: Biomedicine & pharmacotherapy Vol. 162; p. 114367
• Main Authors: Hashemian, Seyed Mohammad Reza, Sheida, Amirhossein, Taghizadieh, Mohammad, Memar, Mohammad Yousef, Hamblin, Michael R., Bannazadeh Baghi, Hossein, Sadri Nahand, Javid, Asemi, Zatollah, Mirzaei, Hamed
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2023; The Authors. Published by Elsevier Masson SAS
• Subjects: 3 C-like protease; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; HIV Protease Inhibitors; Humans; Nirmatrelvir; Pandemics; Paxlovid; Peptide Hydrolases; Review; Ritonavir; SARS-CoV-2; COVID-19; Paxlovid; SARS-CoV-2; Nirmatrelvir; Ritonavir; 3 C-like protease
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2023.114367

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. [Display omitted] •Nirmatrelvir/ritonavir is used as an emergency therapy for mild-to-moderate COVID-19.•Nirmatlavir can inhibit the main protease (Mpro) of SARS-CoV-2.•Ritonavir increases plasma concentrations of nirmatrelvir by targeting CYP3A4.•Interaction between nirmatrelvir/ritonavir and other drugs needs more studies.•Paxlovid's low cost and easy administration can become it’s a tool in fighting virus.