Repurposed nasal antibiotic neomycin shows promise in preventing and treating respiratory viral infections

In a recent study published in the journal Proceedings of the National Academy of SciencesA team of researchers from Yale School of Medicine and Harvard University used mouse models to show that intranasally administered neomycin sulfate was effective against viruses such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated whether it could induce antiviral protection against respiratory viruses. Induces expression of ISG or interferon-stimulated genes.

study: Intranasal administration of neomycin induces broad-spectrum antiviral immunity in the upper respiratory tract. Image credit: TG23 / Shutterstock

background

Respiratory viruses are a group of pathogens belonging to numerous virus families that pose a serious threat to human health because they are transmitted primarily through droplets and aerosolized respiratory secretions. The gravity of the threat from respiratory viruses was highlighted by the coronavirus disease 2019 (COVID-19) pandemic, in which SARS-CoV-2 has claimed nearly 7 million lives and infected more than 700 million people worldwide. Became. In addition, influenza viruses cause 500,000 deaths and 5 million people, respectively, worldwide each year.

However, despite significant advances in the development of vaccines and treatments for respiratory viruses, these pathogens remain a serious public health concern. The availability of drugs to treat respiratory viral infections is also inequitable worldwide. In addition, antiviral drugs, immunomodulatory drugs, convalescent plasma Monoclonal antibodies only reduce disease progression after infection has been established and are not used as prophylaxis or treatment to stop infection before it progresses to the lower respiratory tract.

About research

In this study, researchers investigated whether intranasal administration of neomycin sulfate or neomycin to mice induces protection against influenza A virus and SARS-CoV-2 by inducing the expression of ISGs. . Neomycin is an aminoglycoside antibiotic that can induce the expression of ISGs. ISGs are effector proteins activated by interferons (IFNs) that interfere with the viral life cycle and prevent viral infection.

Respiratory viral infections are often severe because the host is unable to induce a timely ISG response in the upper respiratory tract and clear the virus before it moves to the lower respiratory tract. Furthermore, therapeutic strategies to initiate ISG-based immune responses against respiratory viruses in the nasal mucosa and upper respiratory tract have also not been well explored.

Here, researchers investigated whether intranasally administered neomycin blocks viral infection in a mouse model, and that topical application of Neosporin, an antibiotic ointment containing neomycin, induces ISG expression in the human nasal mucosa. I considered whether or not.

Mice were treated intranasally with 2 mg neomycin, nasal turbinate tissue was collected from euthanized mice, and ISG expression was assessed using ribonucleic acid (RNA) fluorescence in situ hybridization. A germ-free mouse model was also treated with neomycin to examine whether neomycin-mediated ISG expression is dependent on the host commensal microbiota. We also measured the secretion levels of interferon types I, II, and III (IFN-α, IFN-β, and IFN-γ, respectively) in the nasal mucosa to determine whether neomycin-mediated ISG expression was affected by neomycin activation. Depends on or not. interferon.

A mouse model of SARS-CoV-2 infection expressing human angiotensin-converting enzyme 2 (ACE-2 receptor) and a mouse model of influenza infection were used to evaluate the preventive efficacy. efficacy of Neomycin was administered intranasally.

result

The researchers reported that intranasal administration of neomycin as a prophylactic or therapeutic option protected mice from upper respiratory tract infections and severe SARS-CoV-2 infection. Intranasal neomycin protected mice infected with a highly virulent influenza A strain from both upper and lower respiratory tract infections.

Neomycin was also found to prevent transmission of SARS-CoV-2 through contact. Furthermore, application of Neosporin ointment was found to induce His ISG expression in the human nasal mucosa, and intranasal administration of neomycin induced He ISG expression in humans and protected against viral infection in the upper respiratory tract mucosa. We have evidence that it is possible.

Furthermore, experiments using germ-free mice showed that neomycin-mediated ISG expression was independent of the role played by commensal bacteria in the host microbiome. Furthermore, interferon was not significantly induced after intranasal administration of neomycin, suggesting that the induction of ISG expression by neomycin is also independent of interferon.

conclusion

Overall, the findings suggested that intranasal administration of neomycin in a mouse model induced strong expression of ISGs that protect against respiratory viruses such as influenza and SARS-CoV-2. Expression of this ISG is independent of host microbiota and interferon-related pathways. These results highlight the potential use of neomycin as a therapeutic or prophylactic agent against respiratory viruses.