The Antiviral Mechanism of Action of Molnupiravir in Humans with COVID-19
Sheahan, T. P.; Stevens, L. J.; Narowski, T. M.; Krajewski, T. J.; Lee, C.; Mollan, K. R.; Gribble, J.; Moreria, F. R.; Castillo, I. N.; Cuadra, E.; Alabanza, P.; James Loftis, A.; Coombs, R. W.; Goecker, E. A.; Greninger, A. L.; Chappell, J. D.; Brown, A. J.; Won, J.; Lipansky, F.; Holman, W.; Szewczyk, L. J.; Baric, R. S.; Painter, W. P.; Eron, J. J.; Premkumar, L.; Denison, M. R.; Fischer, W. A.
Show abstract
Meaningful metrics of antiviral activity are essential for determining the efficacy of therapeutics in human clinical trials. Molnupiravir (MOV) is a broadly acting antiviral nucleoside analog prodrug that acts as a competitive alternative substrate for the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We developed an assay, Culture-PCR, to better understand the impact of MOV therapy on infectious SARS-CoV-2. Culture-PCR revealed MOV eliminated infectious virus within 48 hours in the nasopharyngeal compartment, the upper airway location with the greatest levels of infectious virus. MOV therapy was associated with increases in mutations across the viral genome but select regions were completely unaffected, thus identifying regions where mutation likely abrogates infectivity. MOV therapy did not alter the magnitude or neutralization capacity of the humoral immune response, a documented correlate of protection. Thus, we provide holistic insights into the function of MOV in adults with COVID-19.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections 96%
- De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: A case report 95%
- Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial 94%
- COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir 94%
- Efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19: the phase 2b part of a randomized, placebo-controlled, phase 2/3 study 93%
Similar papers in this journal
- Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants 94%
- Reduced Pathogenicity of the SARS-CoV-2 Omicron Variant in Hamsters 94%
- Omicron neutralizing antibody response following booster vaccination compared with breakthrough infection 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.