A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients.

Autor: Alteri C; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Fox V; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Scutari R; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Burastero GJ; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Volpi S; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Faltoni M; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Fini V; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy., Granaglia A; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy., Esperti S; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Gallerani A; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Costabile V; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy., Fontana B; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Franceschini E; Department of Infectious Diseases, AOU Modena, Modena, Italy., Meschiari M; Department of Infectious Diseases, AOU Modena, Modena, Italy., Campana A; Academic Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Bernardi S; Academic Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Villani A; Academic Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Bernaschi P; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy., Russo C; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy., Guaraldi G; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Mussini C; Department of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy., Perno CF; Multimodal Research Area, Microbiology and Diagnostics of Immunology Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy. carlofederico.perno@opbg.net.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Dec 15; Vol. 5 (1), pp. 1376. Date of Electronic Publication: 2022 Dec 15.
DOI: 10.1038/s42003-022-04322-8
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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