A dengue virus inhibitor that is shown to be effective in mouse models of infection is described in a study published this week in Nature. The findings also shed light on a novel mechanism of antiviral action for future development of dengue therapeutic agents.
Dengue, a mosquito-borne viral disease, is reported to affect around 96 million people every year, with an estimated 3.9 billion people at risk of infection, and the incidence numbers have been growing rapidly in recent decades. There are no antiviral agents for the prevention or treatment of dengue; the virus has multiple variants, so finding a universal dengue therapeutic agent has proved challenging.
Johan Neyts and colleagues used a large-scale screen to identify compounds that inhibit dengue virus in cell culture. The most promising compound was then optimized to a compound (called JNJ-A07) that is highly potent against all known subtypes of dengue virus. The compound has a favourable safety profile in mice and rats, and is shown to reduce viral load in mice models of infection when administered orally, both as prevention and treatment. The authors found that JNJ-A07 interferes with virus replication by blocking the interaction of two viral proteins (NS3 and NS4B), revealing an entirely new mechanism of antiviral action.
“Although JNJ-A07 is not the first dengue NS4B inhibitor to be discovered, it is one of the most promising and well characterized” write Scott B. Biering and Eva Harris in an accompanying News & Views. They emphasize that more questions need to be answered when planning clinical trials in humans in the future, but “the fact that they can now even be considered represents a major advance in the field of dengue therapeutics.”
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