Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model

Abstract

The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity, identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta VOCs and Omicron in the Syrian hamster COVID-19 model. Omicron replication and associated lung disease in vehicle treated hamsters was reduced compared to the earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of Alpha, Beta and Delta VOC infected hamsters. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious virus titers compared to viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants.

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“…The current treatment plan for non-hospitalized COVID-19 patients involves remdesivir and monoclonal antibodies like sotrovimab; however, these treatments require complex parenteral administration and are expensive. [2] Molnupiravir, being oral and also effective against newer COVID-19 variants, [8] is more practical and convenient for administration in ambulatory patients fulfilling the unmet need for safe and effective oral drugs in this population. [9] The huge reduction in the risk of mortality observed in our meta-analysis is highly encouraging.…”

SARS‐CoV‐2 Omicron and its current known unknowns: A narrative review

“… 13 Research suggests that certain monoclonal antibodies may be less potent or even non‐effective in treating Omicron, while some remain susceptible to its treatment (Table 2 ). 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 …”