Intranasal neomycin evokes broad- spectrum antiviral immunity in the upper respiratory tract

• 成果类型: Article
• 署名作者: Mao, Tianyang; Kim, Jooyoung; Pena-Hernandez, Mario A.; Valle, Gabrielee; Moriyama, Miyu; Luyten, Sophia; Ott, Isabel M.; Gomez-Calvo, Maria Luisa; Gehlhausen, Jeff R.; Baker, Emily; Israelow, Benjamin; Slade, Martin; Sharma, Lokesh; Liu, Wei; Ryu, Changwan; Korde, Asawari; Lee, Chris J.; Monteiro, Valter Silva; Lucas, Carolina; Dong, Huiping; Yang, Yi; Gopinath, Smita; Wilen, Craig B.; Palm, Noah; Cruz, Charles S. Dela; Iwasaki, Akiko
• 署名单位: Yale University; Yale University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Yale University; Yale University; Yale University; Yale University; Harvard University; Harvard T.H. Chan School of Public Health; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Pittsburgh Healthcare System; Yale University; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14201
• DOI: 10.1073/pnas.2319566121
• 发表日期: 2024-04-30
• 关键词: polymyxin-b; systematic analysis; global burden; 195 countries; interferon; territories; induction; infection; responses; disease

摘要

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.