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

J Med Virol. 2024 Sep;96(9):e29901. doi: 10.1002/jmv.29901.

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.

Keywords: SARS‐CoV‐2; antiviral; hamster; interferon; molnupiravir.

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Cricetinae
  • Cytidine / analogs & derivatives
  • Cytidine / pharmacology
  • Cytidine / therapeutic use
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Hydroxylamines* / pharmacology
  • Hydroxylamines* / therapeutic use
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Interferons / therapeutic use
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Leucine / therapeutic use
  • Lung* / drug effects
  • Lung* / pathology
  • Lung* / virology
  • Male
  • Mesocricetus*
  • SARS-CoV-2* / drug effects
  • Viral Load* / drug effects
  • Virus Replication* / drug effects

Substances

  • Antiviral Agents
  • molnupiravir
  • Hydroxylamines
  • Cytidine
  • Interferon-alpha
  • Cytokines
  • Interferons
  • Leucine