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

Abstract

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 <b>JNJ-1802</b> 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 <b>JNJ-1802</b> 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. <b>JNJ-1802</b> is being progressed in clinical studies for the prevention or treatment of dengue.