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Proc Natl Acad Sci U S A
. 2024 Apr 30;121(18):e2319566121.
doi: 10.1073/pnas.2319566121. Epub 2024 Apr 22. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Tianyang Mao # 1 , Jooyoung Kim # 2 3 , Mario A Peña-Hernández # 1 4 , Gabrielee Valle 2 , Miyu Moriyama 1 , Sophia Luyten 1 , Isabel M Ott 1 , Maria Luisa Gomez-Calvo 1 , Jeff R Gehlhausen 5 , Emily Baker 5 , Benjamin Israelow 1 6 , Martin Slade 7 , Lokesh Sharma 2 3 , Wei Liu 2 , Changwan Ryu 2 , Asawari Korde 2 , Chris J Lee 2 , Valter Silva Monteiro 1 , Carolina Lucas 1 , Huiping Dong 1 , Yi Yang 1 ; Yale SARS-CoV-2 Genomic Surveillance Initiative; Smita Gopinath 8 , Craig B Wilen 1 9 , Noah Palm 1 , Charles S Dela Cruz 2 3 10 , Akiko Iwasaki 1 5 11 12
Affiliations
Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.
Keywords: antiviral; interferon; mucosal immunity; nasal; transmission.
. 2024 Apr 30;121(18):e2319566121.
doi: 10.1073/pnas.2319566121. Epub 2024 Apr 22. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Tianyang Mao # 1 , Jooyoung Kim # 2 3 , Mario A Peña-Hernández # 1 4 , Gabrielee Valle 2 , Miyu Moriyama 1 , Sophia Luyten 1 , Isabel M Ott 1 , Maria Luisa Gomez-Calvo 1 , Jeff R Gehlhausen 5 , Emily Baker 5 , Benjamin Israelow 1 6 , Martin Slade 7 , Lokesh Sharma 2 3 , Wei Liu 2 , Changwan Ryu 2 , Asawari Korde 2 , Chris J Lee 2 , Valter Silva Monteiro 1 , Carolina Lucas 1 , Huiping Dong 1 , Yi Yang 1 ; Yale SARS-CoV-2 Genomic Surveillance Initiative; Smita Gopinath 8 , Craig B Wilen 1 9 , Noah Palm 1 , Charles S Dela Cruz 2 3 10 , Akiko Iwasaki 1 5 11 12
Affiliations
- PMID: 38648490
- DOI: 10.1073/pnas.2319566121
Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.
Keywords: antiviral; interferon; mucosal immunity; nasal; transmission.