Jerusalem, 4 August, 2025 (TPS-IL) — A new antiviral drug pairing—featuring a compound found in chocolate — has outperformed Tamiflu in preclinical trials and could mark a turning point in the fight against influenza, including its deadliest and most drug-resistant strains, israeli scientists announced on Monday.
The study, published in the peer-reviewed Proceedings of the National Academy of Sciences (PNAS), was led by Professor Isaiah (Shy) Arkin of the Hebrew University of Jerusalem. His team discovered that a combination of Theobromine, a natural compound found in cocoa, and Arainosine, a little-known molecule originally developed for other uses, can block a critical internal mechanism in the influenza virus that Tamiflu cannot reach.
“We’re not just offering a better flu drug,” Arkin said. “We’re introducing a completely different way to target viruses—one that bypasses the usual mutation traps and could apply to many future threats.”
Since its approval by the FDA in 1999, Tamiflu has become a frontline treatment for seasonal flu in many countries. Also known as Oseltamivir, it works by targeting a surface protein on the virus that frequently mutates, allowing the virus to develop resistance over time.
But instead of chasing that shifting target, Arkin’s team focused on a structural weak point: the M2 ion channel, a tiny gate within the virus that controls its ability to replicate. Blocking this internal channel cuts the virus off at its source.
Attempts to exploit this vulnerability in the past have failed, as the virus quickly developed resistance to early M2 inhibitors. But the new Theobromine-Arainosine combo appears to bypass that resistance, showing remarkable results in both lab cultures and animal models, including against strains of avian and swine flu that no longer respond to existing antivirals, the researchers said.
The breakthrough was made possible using a bacteria-based screening method developed by Arkin’s lab, which scanned hundreds of repurposed compounds — substances originally designed to treat other conditions. Theobromine and Arainosine stood out not just for their effectiveness, but for how powerfully they worked together to block the virus’s ion channel.
“In our tests, this combination didn’t just slow the virus—it shut it down,” Arkin said.
The discovery comes at a time of growing concern over influenza’s evolving threat. In the U.S. alone, seasonal flu costs an estimated $87 billion annually in medical expenses and lost productivity. More severe outbreaks—like the 2009 swine flu pandemic—have inflicted global damage in the hundreds of billions. Recent waves of avian flu have also decimated poultry industries, raising fears of human spillover.
Adding to the urgency, Tamiflu and other conventional antivirals are losing ground as flu viruses mutate. That’s what makes the new strategy so significant: rather than attacking the parts of the virus that mutate rapidly, Arkin’s team has found a way to strike at its more conserved and essential functions.
Even more promising is the possibility that this method could work against other viruses. “Ion channels aren’t unique to influenza,” Arkin explained. “Many viruses, including coronaviruses, rely on similar mechanisms to survive. This could be the foundation for a new class of broad-spectrum antivirals.”
The study’s findings offer immediate clinical potential in the fight against influenza. The Theobromine-Arainosine drug combination could provide a more effective alternative to Tamiflu, especially against drug-resistant strains such as H1N1 swine flu and H5N1 bird flu. By targeting the virus’s M2 ion channel — a structure less prone to mutation — the treatment bypasses common resistance mechanisms, potentially reducing hospitalizations, complications, and deaths during seasonal outbreaks or pandemics.
Beyond flu treatment, the research opens the door to broader antiviral applications. Since many viruses, including coronaviruses, rely on similar ion channels to replicate, the strategy could form the basis for a new class of broad-spectrum antivirals.
The next step is human clinical testing. To that end, a new biotech startup called ViroBlock, spun out of Hebrew University, has been tasked with developing the treatment for eventual public use.
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