Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV
Date
2025-03
Authors
Rajabali Zadeh, Vahid
Lew, Jocelyne M.
Zahoor, Muhammad Atif
Santer, Deanna
Feld, Jordan J.
Falzarano, Darryl
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Elsevier
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Article
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Abstract
Therapeutic options against pathogenic human coronaviruses remain limited. In a recent clinical trial, we demonstrated the therapeutic efficacy of pegylated-IFN-λ in COVID-19 outpatients. However, the emergence of variants that have the potential to evade IFN-mediated antiviral responses raises concerns regarding the continued efficacy of this approach. In this work, we compared the sensitivity of SARS-CoV-2 variants and MERS-CoV to IFN-λ treatment in vitro and explored the potential of combination therapy with other FDA-authorized or approved antiviral agents. We observed that in contrast to the ancestral strain, all other SARS-CoV-2 lineages showed varying, but increased resistance to IFN-λ treatment, from a 5.7-fold increase in EC50 value for the P.1 strain to a 32.7-fold increase for the B.1.1.7 variant. We further show that combination treatment with remdesivir or nirmatrelvir enhanced the antiviral effect of IFN-λ against both SARS-CoV-2 and MERS-CoV. These findings justify the initiation of further in vivo testing that ultimately can help inform the development of more effective therapeutic guidelines against pathogenic coronaviruses.
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Keywords
SARS-CoV-2, MERS-CoV, Interferon lambda, Therapeutics, Variants of concern
Citation
Zadeh, V. R., Lew, J. M., Zahoor, M. A., Santer, D., Feld, J. J., & Falzarano, D. (2025). Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV. Virus Research, 355, 199560-. https://doi.org/10.1016/j.virusres.2025.199560
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DOI
https://doi.org/10.1016/j.virusres.2025.199560