A surprising new drug combination—including a compound found in chocolate—has outperformed Tamiflu in fighting flu, according to a study published in PNAS. The mix of theobromine and arainosine proved far more effective against a range of influenza strains, including drug-resistant variants of bird and swine flu.
By targeting a key viral weakness, this breakthrough could pave the way for stronger, longer-lasting treatments for flu—and potentially for other viruses as well.
In a significant development for flu treatment, scientists have introduced a new drug pairing that surpasses Tamiflu, currently the most widely used anti-influenza medicine, even against the deadliest strains such as avian and swine flu. The duo? One of them is theobromine, a well-known compound found in chocolate.
In the study—recently published in the Proceedings of the National Academy of Sciences (PNAS)—researchers at the Hebrew University of Jerusalem, led by Professor Isaiah (Shy) Arkin, developed a novel combination therapy targeting a critical vulnerability in the influenza virus: its ion channel, a microscopic “gate” the virus relies on to reproduce and spread. By blocking this gate, the team was able to effectively halt the virus’s ability to survive.
Conducted at Israel’s new Barry Skolnick Biosafety Level 3 facility, the research tested the combination—theobromine and a lesser-known compound called arainosine—against a broad array of flu viruses. In both laboratory and animal trials, the treatment dramatically outperformed oseltamivir (Tamiflu), particularly when tested against drug-resistant strains.
“We’re not just offering a better flu drug,” said Professor Arkin. “We’re introducing a new way to target viruses—one that may help us prepare for future pandemics.”
Why This Matters
The stakes are high: influenza still sweeps the globe each year, with unpredictable mutations that challenge current vaccines and treatments. In the US alone, seasonal flu costs an estimated $87 billion annually in healthcare and lost productivity. Previous pandemics, like the 2009 swine flu, exacted even greater costs, and the projected cost of future pandemics could rise to $4.4 trillion.
Meanwhile, outbreaks of avian flu continue to devastate poultry industries and spark global concern over cross-species transmission. One recent outbreak in the US led to the loss of 40 million birds and billions of dollars in damage.
Current flu treatments such as Tamiflu are becoming less effective as the virus adapts. Most antivirals target a viral protein that mutates rapidly, often making existing drugs obsolete. That’s where Arkin and his team saw a new opportunity.
A New Approach to Old Viruses
Rather than attacking the virus in the traditional way, the researchers focused on the M2 ion channel—a crucial viral feature for replication. Previous efforts to block this channel have largely failed due to drug resistance. However, the new theobromine-arainosine combination sidesteps this hurdle, neutralising even hard-to-treat strains.
The combination was discovered through screening a library of repurposed compounds—many initially intended for other diseases—and testing their effects on both drug-sensitive and drug-resistant flu strains.
Broader Implications
The implications extend beyond influenza. Many viruses—including coronaviruses—also rely on ion channels, so this innovative approach could underpin future antiviral strategies.
While the next steps include human clinical trials, these early results offer hope not only for improved flu treatment, but also for smarter ways to combat viral disease in general. ViroBlock, a startup spun out from the Hebrew University, is now working to bring these discoveries to the public.
The research paper, “A Bacteria-Based Search for Drugs Against Avian and Swine Flu Yields a Potent and Resistance-Resilient Channel Blocker,” is now available in PNAS and can be accessed at https://doi.org/10.1073/pnas.2502240122.
Researchers:
Hiya Lahiri, Eitan Israeli, Miriam Krugliak, Kingshuk Basu, Yelena Britan-Rosich, Tamar Ravins Yaish, and Professor Isaiah T. Arkin
Institutions:
- Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem
- Barry Skolnick Biosafety Level 3 Unit, Hebrew University of Jerusalem
- Authority for Biological and Biomedical Models, Hebrew University of Jerusalem