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- Title
A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients.
- Authors
Alteri, Claudia; Fox, Valeria; Scutari, Rossana; Burastero, Giulia Jole; Volpi, Sara; Faltoni, Matteo; Fini, Vanessa; Granaglia, Annarita; Esperti, Sara; Gallerani, Altea; Costabile, Valentino; Fontana, Beatrice; Franceschini, Erica; Meschiari, Marianna; Campana, Andrea; Bernardi, Stefania; Villani, Alberto; Bernaschi, Paola; Russo, Cristina; Guaraldi, Giovanni
- Abstract
Little is known about SARS-CoV-2 evolution under Molnupiravir and Paxlovid, the only antivirals approved for COVID-19 treatment. By investigating SARS-CoV-2 variability in 8 Molnupiravir-treated, 7 Paxlovid-treated and 5 drug-naïve individuals at 4 time-points (Days 0-2-5-7), a higher genetic distance is found under Molnupiravir pressure compared to Paxlovid and no-drug pressure (nucleotide-substitutions/site mean±Standard error: 18.7 × 10−4 ± 2.1 × 10−4 vs. 3.3 × 10−4 ± 0.8 × 10−4 vs. 3.1 × 10−4 ± 0.8 × 10−4, P = 0.0003), peaking between Day 2 and 5. Molnupiravir drives the emergence of more G-A and C-T transitions than other mutations (P = 0.031). SARS-CoV-2 selective evolution under Molnupiravir pressure does not differ from that under Paxlovid or no-drug pressure, except for orf8 (dN > dS, P = 0.001); few amino acid mutations are enriched at specific sites. No RNA-dependent RNA polymerase (RdRp) or main proteases (Mpro) mutations conferring resistance to Molnupiravir or Paxlovid are found. This proof-of-concept study defines the SARS-CoV-2 within-host evolution during antiviral treatment, confirming higher in vivo variability induced by Molnupiravir compared to Paxlovid and drug-naive, albeit not resulting in apparent mutation selection. A proof-of-concept study on the genomic evolution of SARS-CoV-2 during antiviral treatment reveals that Molnupiravir induces a higher in vivo intra-host variability compared to Paxlovid and drug-naive.
- Subjects
RNA replicase; SARS-CoV-2; COVID-19 treatment; MOLNUPIRAVIR; GENETIC distance
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-04322-8