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

antiviral interferon mucosal immunity nasal transmission

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
30 Apr 2024
Historique:
medline: 23 4 2024
pubmed: 23 4 2024
entrez: 22 4 2024
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 38648490
doi: 10.1073/pnas.2319566121
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2319566121

Subventions

Organisme : Bill and Melinda Gates Foundation (GF)
ID : N/A
Organisme : Howard Hughes Medical Institute (HHMI)
ID : N/A

Déclaration de conflit d'intérêts

Competing interests statement:A.I. co-founded and consults for RIGImmune, Xanadu Bio and PanV, consults for Paratus Sciences, InvisiShield Technologies, and is a member of the Board of Directors of Roche Holding Ltd.

Auteurs

Tianyang Mao (T)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Jooyoung Kim (J)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh PA 15213.

Mario A Peña-Hernández (MA)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven CT 06510.

Gabrielee Valle (G)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.

Miyu Moriyama (M)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Sophia Luyten (S)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Isabel M Ott (IM)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Maria Luisa Gomez-Calvo (ML)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Jeff R Gehlhausen (JR)

Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.

Emily Baker (E)

Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.

Benjamin Israelow (B)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510.

Martin Slade (M)

Department of Internal Medicine, Section of Occupational Medicine, Yale University School of Medicine, New Haven, CT 06510.

Lokesh Sharma (L)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh PA 15213.

Wei Liu (W)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.

Changwan Ryu (C)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.

Asawari Korde (A)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.

Chris J Lee (CJ)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.

Valter Silva Monteiro (V)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Carolina Lucas (C)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Huiping Dong (H)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Yi Yang (Y)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Smita Gopinath (S)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115.

Craig B Wilen (CB)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510.

Noah Palm (N)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.

Charles S Dela Cruz (CS)

Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, CT 06510.
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh PA 15213.
Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240.

Akiko Iwasaki (A)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
Center for Infection and Immunity, Yale University School of Medicine, New Haven, CT 06510.
HHMI, Chevy Chase, MD 20815.

Classifications MeSH