New Drug Combination Shows Promise Against Resistant Influenza Strains

Influenza remains a persistent world health threat, with yearly outbreaks and the ever-present danger of animal-to-human spread, such as bird flu A(H5N1)—creating significant challenges for public health care systems. The standard treatment often used is neuraminidase blockers like oseltamivir (Tamiflu; Roche), but there have been cases of this not effectively working in severe infections.¹ This points out the urgent need for new treatments that fight the virus in new ways and offer a higher barrier to resistance.

Discovery of a Novel Combination

A study in the Proceedings of the National Academy of Sciences (PNAS) introduced a new approach to antiviral discovery. Scientists made a system using bacteria to identify compounds that inhibit the influenza A M2 proton channel, which is vital for viral replication.² In the past, aminodamantane drugs such as amantadine and rimantadine targeted this channel. But changes in the virus, like S31N, interrupt their efficacy. Using their bacteria setup, investigators discovered 2 drugs—arainosine and theobromine—that work well together and fight influenza strains well in both cell and animal models.²

Preclinical data showed that the combination protected cultured cells from infection and greatly cut down viral loads and illness severity in mice. Notably, this treatment remained effective on types of the virus that did not improve with the old M2 inhibitors and showed superior results to oseltamivir. This shows that blocking the M2 channel, which people once thought was dated, may reemerge as a way to treat the illness if it’s used with the right molecular partners.

Translational Potential

An institutional summary from the Hebrew University of Jerusalem emphasized the translational significance of this discovery. The report said that one of the compounds, theobromine, commonly found in chocolate, shows how well-known molecules can be used in new ways to fight viruses. The press release also stated that these 2 drugs did better than oseltamivir in preclinical tests of bird and swine flu, and development efforts are already underway with a new university-affiliated company, ViroBlock.³ Although clinical testing has not begun, the plan to pursue human trials shows a strong push forward in this field.

Implications for Pharmacists

For pharmacists, these findings represent current and future opportunities. The usual standards for treating patients with suspected or confirmed severe influenza remain the same: if a patient has suspected or confirmed severe influenza, they should receive oseltamivir promptly, and clinicians may consider combination therapy in consultation with infectious disease specialists when resistance is suspected.¹ Pharmacists may remind patients that experimental combinations like theobromine–arainosine are not yet approved to use and that taking OTC products on their own is not a safe or effective way to treat influenza.

Moving forward, pharmacists should monitor the progress of this drug combination as it advances. A treatment that blocks M2 channels and fights off resistance could expand the antiviral toolkit for fighting viruses and potentially cut down on sole reliance on neuraminidase blockers. Pharmacists will play a key role in educating patients, monitoring drug-drug interactions, and clarifying the distinct mechanism of action should this therapy reach the market.

Conclusion

Although still in early stages, the discovery of an M2 channel–blocking drug combination offers a promising path forward in the fight against resistant influenza strains. By leveraging bacterial screening methods, researchers have identified a therapy that may overcome long-standing resistance issues while outperforming existing antivirals in preclinical studies.²^,³ Until human trials confirm safety and efficacy, pharmacists must continue to emphasize evidence-based current treatments and remain informed on the potential arrival of a new class of influenza therapeutics.

REFERENCES

1. CDC. Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease. Avian Influenza (Bird Flu). Published July 8, 2025. https://www.cdc.gov/bird-flu/hcp/clinicians-evaluating-patients/interim-guidance-treatment-humans.html

2. Lahiri H, Israeli E, Krugliak M, et al. A bacteria-based search for drugs against avian and swine flu yields a potent and resistance-resilient channel blocker. Proceedings of the National Academy of Sciences. 2025;122(31). doi:10.1073/pnas.2502240122

3. Huji.ac.il. Published 2025. https://en.huji.ac.il/news/new-drug-combo-outperforms-tamiflu-fighting-flu