How a rare disease could produce a drug against the pandemic

Vviruses are all around us. These pathogens can sneak past our immune systems and bombard us with infections that leave us exposed for days or weeks. While some viruses eventually go away on their own, others can cause serious illness or even death. Even today, the flu kills between 3,000 and 50,000 people per year in the United States, especially children and the elderly. And of course, COVID-19 has claimed millions of lives around the world. It seems that every two or three years a highly contagious, often fatal, viral disease emerges, leading to a new epidemic.

Until now, scientists have struggled to identify compounds that could be used as universal antivirals, capable of fighting large numbers of viral infections in one fell swoop. But recently, scientists have drawn inspiration for such a superdrug from a quiet corner of the medical world: the small subset of people with a rare autoimmune disease called ISG15 deficiency, for whom viruses have almost no impact.

This autoimmune disease, which typically affects infants and young children, is caused by a deficiency of an immune system regulatory molecule called, unsurprisingly, ISG15. The deficiency creates a state of persistent low-level inflammation in the body that can lead to skin lesions, neurological complications and adverse reactions to certain vaccines. But this inflammation also has an advantage: it protects these patients against most viral infections.

Dusan Bogunovic, a pediatric immunologist at Columbia University, and some of his colleagues recently decided to study whether they could harness this power to protect people who don’t do it have trouble with a viral infection. In August, they published their findings in the journal Scientific translational medicine. In this experimental work, the team tested a potential drug on human cells as well as mice and hamsters and found that it provided protection against a number of viruses, including those that cause Zika, COVID-19 and certain strains of flu. This drug could even play a crucial role in mitigating infections by unknown viruses during the next global pandemic, Bogunovic says.

Although the drug would work similarly to a vaccine to provide preemptive immunity, Bogunovic says the mechanism is actually very different. Instead of introducing an inactivated virus or a small piece of virus, as vaccines typically do, this approach would introduce genes already naturally synthesized in the human body.

The drug could even play a crucial role in mitigating infections from unknown viruses during the next global pandemic.

“What we did was basically synthesize genes that our body normally synthesizes,” Bogunovic says. “There is no class of drugs where we are essentially using our own genetic code… to combat our viral functions. »

When a person is exposed to a virus in nature, it can trigger thousands of genetic responses, Bogunovic says. This is part of what makes us feel so lousy. To create a low-level inflammatory response that mimics that of ISG15 deficiency, the research team isolated just 10 genes that are most crucial for initiating this inflammatory response. Using mRNA techniques, these genes were then integrated into a lipid nanoparticle that will be deployed first in a human cell culture and then in animal models.

In their first test on human cells, Bogunovic says they observed a much higher immune response than placebo alone. It was an “oh wow” moment, he said.

The team then moved on to animal trials where they gave groups of mice and hamsters a strain of influenza and SARS-CoV-2 (which causes COVID-19), respectively. Part of each group of animals then received the antiviral drug while the other part received a placebo drug. In these trials, mice that took the antiviral had 1,000 times greater protection against the flu virus than the placebo alone, Bogunovic says. But the hamsters fared even better.

“Basically, we gave [the] The hamsters had so much virus that those who received the placebo started to die,” he says. The hamsters who received their drugs, on the other hand, had a slight illness but were later cured.

Carl Nathan, a professor of medicine at Weill Cornell Medicine who was not involved in this research, said the results are promising. “The result [of this research] “This is a resounding vindication of efforts to comprehensively study people with rare diseases,” says Nathan. “The potential for medical benefit is high.” Megan Cooper, a professor of pediatric rheumatology at Washington University in St. Louis, who was also not involved in the research, agrees, given the lack of existing universal therapies to treat viral infections.

In the future, Bogunovic envisions the drug as something a person can take weekly, or even monthly, via an inhaler or topical cream to protect against almost any virus. However, there are certain obstacles to achieving this future, both scientific and societal.

Both Nathan and Cooper agree that safety and effectiveness will need to be tested in future human trials. In particular, researchers will need to ensure that these 10 genes do not produce a toxic effect when delivered via the mRNA-made nanoparticle, Nathan says.

But Bogunovic worries that in an anti-mRNA and anti-vaccine political climate, it will be difficult to advance this drug as a potential tool to fight the next pandemic.

“In the context of the development of anti-infectives and antivirals, it became clear that we really need government and state support to make this a reality,” says Bogunovic. “Market forces alone are not enough. »

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Main image: Vectorfair / Shutterstock

• Sarah Wells

  Published on October 15, 2025

  Sarah Wells is a freelance science writer. His work appeared in Nature, Popular Mechanics, National Geographic And Scientific news explores. You can learn more about her writing on her website: https://saraheswells.com/