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.

Alteri, C., Fox, V., Scutari, R., Burastero, G.j., Volpi, S., Faltoni, M., et al. (2022). A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients. COMMUNICATIONS BIOLOGY, 5(1), 1-12 [10.1038/s42003-022-04322-8].

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

Villani A.;
2022-01-01

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.
2022
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
English
Alteri, C., Fox, V., Scutari, R., Burastero, G.j., Volpi, S., Faltoni, M., et al. (2022). A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients. COMMUNICATIONS BIOLOGY, 5(1), 1-12 [10.1038/s42003-022-04322-8].
Alteri, C; Fox, V; Scutari, R; Burastero, Gj; Volpi, S; Faltoni, M; Fini, V; Granaglia, A; Esperti, S; Gallerani, A; Costabile, V; Fontana, B; Franceschini, E; Meschiari, M; Campana, A; Bernardi, S; Villani, A; Bernaschi, P; Russo, C; Guaraldi, G; Mussini, C; Perno, Cf
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 2.16 MB
Formato Adobe PDF
2.16 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/317317
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 10
social impact