PAXLOVID™ (PF-07321332; ritonavir)

Paxlovid is a novel, COVID-19, oral, antiviral candidate. PAXLOVID™ is a SARS-CoV-2-3CL protease (an enzyme that the coronavirus needs to replicate) inhibitor, which originated in Pfizer’s laboratories. It may have efficacy as a prophylaxis and/or outpatient treatment. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of PF-07321332 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.

• 22 December 2021: EUA in the USA for patients 12 years of age and older weighing at least 40 kg with mild-to-moderate COVID-19, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

The Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) study began enrollment in July 2021.
The Phase 2/3 EPIC-SR (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) and EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) studies, began in August and September 2021 respectively.

Adverse events in the PAXLOVID group (≥1%) that occurred at a greater frequency (≥5 subject difference) than in the placebo group were dysgeusia (6% and <1%, respectively), diarrhea (3% and 2%), and hypertension (1% and <1%), and myalgia (1% and <1%). The proportions of subjects who discontinued treatment due to an adverse event were 2% in the PAXLOVID group and 4% in the placebo group.

Editorial: Safety and efficacy of antivirals against SARS-CoV-2
Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332
Supervised Molecular Dynamics (SuMD) Insights into the mechanism of action of SARS-CoV-2 main protease inhibitor PF-07321332
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The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
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Computational simulations on the binding and reactivity of a nitrile inhibitor of the SARS-CoV-2 main protease†

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