Researchers identify first drug that is effective against dengue infection

Belgium: A recent study reported in the journal Nature has described a new target for the treatment of dengue. The antiviral compound showed strong activity in mice for prophylaxis against dengue and for treatment of the infection. 

The target was identified by researchers at KU Leuven Rega Institute and Center for Drug Design and Discovery (CD3), Leuven, Belgium in collaboration with Jannsen Pharmaceutica, NV. 

Dengue is a viral infection that is spread to people through the bite of an Aedes mosquito. Dengue virus affects about 96 million symptomatic infections annually manifesting as dengue fever or occasionally as severe dengue. As of now, there is no availability of antiviral agents for preventing or treating dengue. The infection is endemic in many tropical and subtropical areas globally, particularly in Asia and Latin America. 

In the study, Marnix Van Loock, Janssen Global Public Health, Janssen Pharmaceutica, Beerse, Belgium, and colleagues described a highly potent dengue virus inhibitor (JNJ-A07) that exerts nanomolar to picomolar activity against a panel of 21 clinical isolates that represent the natural genetic diversity of known genotypes and serotypes.

"The molecule has a high barrier to resistance and prevents the formation of the viral replication complex by blocking the interaction between two viral proteins (NS3 and NS4B), thus revealing a previously undescribed mechanism of antiviral action," wrote the authors. "JNJ-A07 has a favorable pharmacokinetic profile that results in outstanding efficacy against dengue virus infection in mouse infection models."

JNJ-A07 was shown to have a favorable pharmacokinetic profile that results in outstanding efficacy against dengue virus infection in mouse infection models. Delaying the start of treatment until peak viremia results in a rapid and significant reduction in viral load. An analog is currently in further development.

Reference:

Kaptein, S.J.F., Goethals, O., Kiemel, D. et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature (2021). https://doi.org/10.1038/s41586-021-03990-6