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ABSTRACT

JNJ-1802—a highly potent dengue virus inhibitor—blocks the NS3–NS4B interaction within the viral replication complex, and is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million^ 1 with annually around 10,000 deaths^ 2 . However, no antiviral drugs are available for the treatment or prophylaxis of dengue. We recently described the interaction between non-structural proteins NS3 and NS4B as a promising target for the development of pan-serotype dengue virus (DENV) inhibitors^ 3 . Here we present JNJ-1802—a highly potent DENV inhibitor that blocks the NS3–NS4B interaction within the viral replication complex. JNJ-1802 exerts picomolar to low nanomolar in vitro antiviral activity, a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes. Finally, we demonstrate that the small-molecule inhibitor JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. JNJ-1802 has successfully completed a phase I first-in-human clinical study in healthy volunteers and was found to be safe and well tolerated^ 4 . These findings support the further clinical development of JNJ-1802, a first-in-class antiviral agent against dengue, which is now progressing in clinical studies for the prevention and treatment of dengue.

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