Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor

Dengue
is a global public health threat, with about half of the
world’s population at risk of contracting this mosquito-borne
viral disease. Climate change, urbanization, and global travel accelerate
the spread of dengue virus (DENV) to new areas, including southern
parts of Europe and the US. Currently, no dengue-specific small-molecule
antiviral for prophylaxis or treatment is available. Here, we report
the discovery of JNJ-1802 as a potent, pan-serotype DENV
inhibitor (EC50’s ranging from 0.057 to 11 nM against
the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in
human hepatocytes, the absence of major in vitro pharmacology safety
alerts, and a dose-proportional increase in efficacy against DENV-2
infection in mice were all supportive of its selection as a development
candidate against dengue. JNJ-1802 is being progressed
in clinical studies for the prevention or treatment of dengue.