Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV
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 conc...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170225000371 |
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| author | Vahid Rajabali Zadeh Jocelyne M. Lew M. Atif Zahoor Deanna Santer Jordan J. Feld Darryl Falzarano |
| author_facet | Vahid Rajabali Zadeh Jocelyne M. Lew M. Atif Zahoor Deanna Santer Jordan J. Feld Darryl Falzarano |
| author_sort | Vahid Rajabali Zadeh |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ca8d272bc1e54b099263747ce6f892f5 |
| institution | DOAJ |
| issn | 1872-7492 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj-art-ca8d272bc1e54b099263747ce6f892f52025-08-20T03:10:29ZengElsevierVirus Research1872-74922025-05-0135519956010.1016/j.virusres.2025.199560Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoVVahid Rajabali Zadeh0Jocelyne M. Lew1M. Atif Zahoor2Deanna Santer3Jordan J. Feld4Darryl Falzarano5Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaToronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada; University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Immunology, University of Manitoba, Winnipeg, MB, CanadaToronto Centre for Liver Disease, University of Toronto, Toronto, ON, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0168170225000371SARS-CoV-2MERS-CoVInterferon lambdaTherapeuticsVariants of concern |
| spellingShingle | Vahid Rajabali Zadeh Jocelyne M. Lew M. Atif Zahoor Deanna Santer Jordan J. Feld Darryl Falzarano Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV Virus Research SARS-CoV-2 MERS-CoV Interferon lambda Therapeutics Variants of concern |
| title | Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV |
| title_full | Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV |
| title_fullStr | Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV |
| title_full_unstemmed | Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV |
| title_short | Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV |
| title_sort | combination therapy enhances the antiviral activity of ifn λ against sars cov 2 and mers cov |
| topic | SARS-CoV-2 MERS-CoV Interferon lambda Therapeutics Variants of concern |
| url | http://www.sciencedirect.com/science/article/pii/S0168170225000371 |
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