tetano
Editor, Senior Moderator
Expert Opin Drug Discov
. 2023 Aug 23;1-11.
doi: 10.1080/17460441.2023.2248879. Online ahead of print. Preclinical discovery and development of nirmatrelvir/ritonavir combinational therapy for the treatment of COVID-19 and the lessons learned from SARS-COV-2 variants
Pasquale Pagliano[SUP] 1 [/SUP], Annamaria Spera[SUP] 1 [/SUP], Carmine Sellitto[SUP] 2 [/SUP], Giuliana Scarpati[SUP] 3 [/SUP], Veronica Folliero[SUP] 4 [/SUP], Ornella Piazza[SUP] 3 [/SUP], Gianluigi Franci[SUP] 4 [/SUP], Valeria Conti[SUP] 2 [/SUP], Tiziana Ascione[SUP] 5 [/SUP]
Affiliations
Introduction: Nirmatrelvir/ritonavir (Paxlovid[SUB]®[/SUB]) represent an oral antiviral therapy approved for the treatment of COVID-19. Extensive in vitro and in vivo studies have reported the promising activity of nirmatrelvir/ritonavir against numerous emerging viruses. This combination consists of nirmatrelvir, a protease reversible inhibitor of coronavirus 3CL[SUP]pro[/SUP] mainly metabolized by cytochrome P450 (CYP)3A4, and ritonavir, an inhibitor of the CYP3A isoforms that enhances the efficacy of nirmatrelvir by fixing its suboptimal pharmacokinetic properties.
Areas covered: This review comprehensively examines the efficacy of nirmatrelvir/ritonavir through rigorous analysis of in vitro and in vivo studies. Moreover, it thoroughly assesses its safety, tolerability, pharmacokinetics, and antiviral efficacy against SARS-COV-2 infection, based on the main pre-authorization randomized controlled trials.
Expert opinion: Nirmatrelvir/ritonavir has a good tolerability profile. Its administration during the early stages of mild-to-moderate COVID-19 holds potential benefits, as it can help prevent the onset of an aberrant immune response that could lead to pulmonary and extra-pulmonary complications. However, its drug - drug interactions can be a factor limiting its use, at least in populations on some chronic therapies, along with the risk of infection relapse after treatment.
Keywords: COVID-19; Nirmatrelvir/ritonavir; Paxlovid; Protease Inhibitor; SARS-CoV-2 variants.
. 2023 Aug 23;1-11.
doi: 10.1080/17460441.2023.2248879. Online ahead of print. Preclinical discovery and development of nirmatrelvir/ritonavir combinational therapy for the treatment of COVID-19 and the lessons learned from SARS-COV-2 variants
Pasquale Pagliano[SUP] 1 [/SUP], Annamaria Spera[SUP] 1 [/SUP], Carmine Sellitto[SUP] 2 [/SUP], Giuliana Scarpati[SUP] 3 [/SUP], Veronica Folliero[SUP] 4 [/SUP], Ornella Piazza[SUP] 3 [/SUP], Gianluigi Franci[SUP] 4 [/SUP], Valeria Conti[SUP] 2 [/SUP], Tiziana Ascione[SUP] 5 [/SUP]
Affiliations
- PMID: 37614103
- DOI: 10.1080/17460441.2023.2248879
Introduction: Nirmatrelvir/ritonavir (Paxlovid[SUB]®[/SUB]) represent an oral antiviral therapy approved for the treatment of COVID-19. Extensive in vitro and in vivo studies have reported the promising activity of nirmatrelvir/ritonavir against numerous emerging viruses. This combination consists of nirmatrelvir, a protease reversible inhibitor of coronavirus 3CL[SUP]pro[/SUP] mainly metabolized by cytochrome P450 (CYP)3A4, and ritonavir, an inhibitor of the CYP3A isoforms that enhances the efficacy of nirmatrelvir by fixing its suboptimal pharmacokinetic properties.
Areas covered: This review comprehensively examines the efficacy of nirmatrelvir/ritonavir through rigorous analysis of in vitro and in vivo studies. Moreover, it thoroughly assesses its safety, tolerability, pharmacokinetics, and antiviral efficacy against SARS-COV-2 infection, based on the main pre-authorization randomized controlled trials.
Expert opinion: Nirmatrelvir/ritonavir has a good tolerability profile. Its administration during the early stages of mild-to-moderate COVID-19 holds potential benefits, as it can help prevent the onset of an aberrant immune response that could lead to pulmonary and extra-pulmonary complications. However, its drug - drug interactions can be a factor limiting its use, at least in populations on some chronic therapies, along with the risk of infection relapse after treatment.
Keywords: COVID-19; Nirmatrelvir/ritonavir; Paxlovid; Protease Inhibitor; SARS-CoV-2 variants.