Abstract

NIRMATRELVIR IN COVID-19 THERAPY: “TARGETING SARS-CoV-2 MAIN PROTEASE”

*Pratham Bohara, Anjali Shinkar

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Abstract

Nirmatrelvir, a potent orally bioavailable 3C-like protease (3CL^pro) inhibitor, represents a significant advancement in the management of COVID-19. Co-administered with ritonavir as Paxlovid, it maintains optimal plasma concentrations by inhibiting CYP3A-mediated metabolism, thereby enhancing antiviral efficacy. Nirmatrelvir prevents viral replication by blocking proteolytic cleavage of SARSCoV- 2 polyproteins, a crucial step in viral maturation. Clinical trials such as EPIC-HR have demonstrated an 88% reduction in hospitalization or death among high-risk, non-hospitalized patients with mild-to-moderate COVID-19 when therapy is initiated within five days of symptom onset. Although generally well tolerated, reported adverse effects include dysgeusia, diarrhoea, and potential drug–drug interactions due to ritonavir’s strong CYP3A inhibition. Regulatory approvals worldwide and its oral route of administration make nirmatrelvir a valuable option for outpatient COVID-19 therapy, enabling early intervention and reducing healthcare burden. Ongoing research explores its role in preventing long COVID and addressing emerging SARS-CoV-2 variants.

Keywords: Nirmatrelvir, Ritonavir, Paxlovid, COVID-19, SARS-CoV-2, 3CL protease inhibitor, antiviral therapy, EPIC-HR trial.