A drug once designed for dengue virus, then quietly abandoned by industry, is suddenly back in the spotlight, and it may be exactly what the global health community has been waiting for. A new study suggests that this antiviral didn’t just slow the dengue virus, it blocked viral replication and significantly reduced infection rates at high doses. Now, scientists are racing to map its path toward clinical trials. If it holds up, this once-side-lined molecule could become the first targeted therapy for a disease that has affected hundreds of millions.
A new study, published in the New England Journal of Medicine, is reviving interest in an antiviral drug called mosnodenvir, originally developed for dengue virus and later shelved by industry. In controlled human challenge trials, the oral compound blocked viral replication and significantly reduced infection rates at high doses, an outcome that has renewed discussion about whether dengue could finally have a targeted treatment. The results arrive amid dengue’s enormous global burden, a disease whose reach and severity are shaped by both how it spreads and how limited current treatments remain.
At its core, dengue is caused by four closely related viruses spread by Aedes mosquitoes. Infection can range from mild flu-like illness to severe disease involving internal bleeding, organ failure, and death. Between 100 million and 400 million people contract dengue annually, primarily in tropical and subtropical regions, and tens of thousands die each year from severe complications. Once the virus takes hold, patients’ options are limited to supportive care, with outcomes ranging from recovery to life-threatening complications and death. Despite the scale of the disease, there are still no approved antiviral treatments.
In the absence of antiviral treatments, vaccines have become the primary tool for reducing dengue risk, but they are not a universal solution. Protective immunity takes time to develop, and some people cannot receive vaccines at all, limiting their usefulness during outbreaks.
Currently, there are three dengue vaccines, yet access and effectiveness remain uneven. One vaccine produced by Sanofi has had a troubled history and is now being discontinued, with the company citing low demand. A second vaccine developed by Japanese manufacturer Takeda was approved in 2022 and is licensed in more than 40 countries, including across the European Union.
More recently, Brazil approved a single-dose dengue vaccine developed by the Butantan Institute. It remains unclear how quickly production can scale or when the vaccine might become available outside the country. Complicating matters further, all existing dengue vaccines rely on weakened live virus, meaning they cannot be given to people who are immunocompromised or pregnant.
That leaves a gap that antivirals could fill. Unlike vaccines, an oral antiviral could be deployed during dengue outbreaks, used prophylactically in endemic regions, or given to travelers and vulnerable populations after exposure. Until now, however, no such treatment has been available.
Mosnodenvir, originally developed by the Janssen Pharmaceutical Companies of Johnson & Johnson, was designed as a broad-spectrum dengue antiviral capable of acting against all four viral serotypes. Rather than targeting the immune response, the drug works inside infected cells, blocking a critical interaction between two viral proteins, NS3 and NS4B. Disrupting that interaction prevents the virus from copying its genetic material, effectively halting replication before infection can take hold.
In laboratory experiments, mosnodenvir showed high potency against a wide range of dengue genotypes, remaining effective at very low concentrations. The drug also performed well in animal models, including mice and nonhuman primates, and showed no major safety concerns in an early human trial.
The strongest evidence came from a controlled human infection model, in which volunteers were deliberately exposed to dengue virus. None of the participants receiving placebo avoided infection. The same was true for those given a low dose of mosnodenvir. Among participants receiving a medium dose, 17% showed no signs of infection. At the highest dose, that number rose to 60%. High-dose treatment also led to a dramatic reduction in viral RNA levels compared with placebo, a difference that was statistically significant.
“It’s one of the most beautiful dose-response results I’ve seen,” said study lead Anna Durbin, to Science.
Despite these results, mosnodenvir did not advance into late-stage clinical development. In October 2024, Johnson & Johnson controversially announced it would end all of its infectious disease research programs, including work on dengue, bringing development of the drug to a halt. The decision was not tied to safety concerns or lack of efficacy, but to a broader shift in research priorities.
Since then, the full results of the controlled human infection study have been published, and encouraging data from two additional trials are now under review. Those studies span more than 30 sites in 10 countries, including the Philippines, Thailand, Peru, Brazil, and Colombia. Even so, mosnodenvir remains in limbo.
“Having watched the development for the last 10 years, I think we were all very disappointed,” noted Sophie Yacoub to Science. Yacoub is a dengue researcher at the University of Oxford, who was not involved in the study.
In a commentary accompanying the New England Journal of Medicine paper, Xuping Xie of the University of Texas Medical Branch notes that oral antivirals could fundamentally change how dengue outbreaks are managed, particularly in regions where vaccination is incomplete or impractical. The situation also highlights a persistent challenge in global health: drugs targeting diseases that disproportionately affect lower-income regions often face higher hurdles to sustained investment, even when early data are strong.
That gap between discovery and deployment is becoming harder to ignore. Dengue is spreading into new regions as climate change expands mosquito habitats, and outbreaks are increasing in both frequency and scale. Access to medicines that can be deployed quickly, without waiting weeks for immunity to develop, is becoming increasingly important.
Because mosnodenvir already has safety data and evidence of efficacy across multiple models, researchers argue that it could move more quickly into further trials than a drug starting from scratch. Durbin believes the science is strong enough to attract renewed interest.
“There is a market, and I think there will be a company that picks it up,” she says.
If that happens, mosnodenvir could become the first targeted antiviral treatment for dengue fever. More broadly, its long and winding path back into the spotlight is a reminder that preparedness depends not only on scientific breakthroughs, but on whether those breakthroughs are carried forward before opportunity is lost.
This study was published in the New England Journal of Medicine.
