Efficacy of molnupiravir and interferon for the treatment of SARS‐CoV‐2 in golden Syrian hamster

Abstract The mortality and hospitalization rate by COVID‐19 dropped significantly currently, but its seasonal outbreaks make antiviral treatment still vital. The mortality and hospitazation rate by COVID‐19 dropped significantly currently, but its seasonal ourbreaks make antiviral treatment still vital. In our study, syrian golden hamsters were treated with molnupiravir and interferons (IFNs) after SARS‐CoV‐2 infection. Their weight changes, pathological changes, virus replication and inflammation levels were evaluated. In the IFNs single treatment, only IFN‐α group reduced viral load ( p < 0.05) and virus titer in hamster lungs. The TNF‐α expression decreased significantly in both IFNs treatment at 2dpi. Histological and immunofluorescence results showed lung damage in the IFNs groups were milder at 4dpi. In the molnupiravir/IFN‐α combination treatment, weight loss and virus replication in lung were significantly decreased in the mono‐molnupiravir group and combination group ( p < 0.05), the expression of IL‐6, TNF‐α, IL‐1β and MIP‐1α also decreased significantly ( p < 0.05), but the combination treatment was not more effective than the mono‐molnupiravir treatment. Histological and immunofluorescence results showed the lung damage and inflammation in mono‐molnupiravir and combination groups were milder. In summary, IFNs treatment had anti‐inflammatory effect against SARS‐CoV‐2, only IFN‐α showed a weak antiviral effect. Molnupiravir/IFN‐α combination treatment was effective against SARS‐CoV‐2 but was not superior to mono‐molnupiravir treatment. IFN‐α could be considered for immunocompromised patients to stimulate and activate early immune responses.