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

Biomed Pharmacother. 2023 Jun:162:114367. doi: 10.1016/j.biopha.2023.114367. Epub 2023 Feb 6.

Abstract

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.

Keywords: 3 C-like protease; COVID-19; Nirmatrelvir; Paxlovid; Ritonavir; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Antiviral Agents
  • COVID-19 Drug Treatment
  • COVID-19*
  • HIV Protease Inhibitors*
  • Humans
  • Pandemics
  • Peptide Hydrolases
  • Ritonavir
  • SARS-CoV-2

Substances

  • nirmatrelvir and ritonavir drug combination
  • Ritonavir
  • Antiviral Agents
  • HIV Protease Inhibitors
  • Peptide Hydrolases