Journal
MEDICINAL CHEMISTRY RESEARCH
Volume 31, Issue 10, Pages 1637-1646Publisher
SPRINGER BIRKHAUSER
DOI: 10.1007/s00044-022-02951-6
Keywords
SARS-CoV-2; Main protease; Paxlovid; Antiviral; Nirmatrelvir
Categories
Funding
- National Institutes of Health (NIH) [AI147325, AI157046, AI158775]
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The rapid development of effective vaccines has decreased hospitalization and mortality rate. However, with the risk of mutated strains, there is an increasing demand for antivirals. Nirmatrelvir is an orally bioavailable antiviral that can be administered in outpatient settings to minimize hospitalizations and death.
The rapid development of effective vaccines to combat the SARS-CoV-2 virus has been an effective counter measure to decrease hospitalization and the mortality rate in many countries. However, with the risk of mutated strains decreasing the efficacy of the vaccine, there has been an increasing demand for antivirals to treat COVID-19. While antivirals, such as remdesivir, have had some success treating COVID-19 patients in hospital settings, there is a need for orally bioavailable, cost-effective antivirals that can be administered in outpatient settings to minimize COVID-19-related hospitalizations and death. Nirmatrelvir (PF-07321332) is an orally bioavailable M-pro (also called 3CL(pro)) inhibitor developed by Pfizer. It is administered in combination with ritonavir, a potent CYP3A4 inhibitor that decreases the metabolism of nirmatrelvir. This review seeks to outline the history of the rational design, the target selectivity, synthesis, drug resistance, and future perspectives of nirmatrelvir. [GRAPHICS] .
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