Antiviral activity of nirmatrelvir against contemporary SARS-CoV-2 variants.

Nirmatrelvir, the active antiviral component of Paxlovid®, was evaluated for potency against 20 genetically diverse and clinically relevant SARS-CoV-2 variants circulating between 2020 and 2024. Robust in vitro antiviral activity was demonstrated against all tested variants, with only modest reductions in susceptibility observed for certain Beta variants. SARS-CoV-2 main protease (Mpro), the target of nirmatrelvir, is conserved among contemporary variants JN.1, XEC, KP.3.1.1, NB.1.8.1, LP.8.1, XFG, and BA.3.2, based on amino acid sequence identity. The key binding residues for nirmatrelvir in Mpro remain highly conserved, supporting its continued effectiveness in the treatment of mild-to-moderate COVID-19. These findings demonstrate that nirmatrelvir maintains antiviral activity across multiple SARS-CoV-2 variants.