JNJ-1802 (Mosnodenvir, JNJ-64281802) is a highly potent, pan-serotype dengue virus (DENV) inhibitor (EC50=0.04  nM-1.8 nM), blocks the NS3-NS4B interaction within the viral replication complex (EC50=1.4 nM, DENV-2).
JNJ-1802 is highly specific for DENV and is inactive against a panel of unrelated DNA and RNA viruses.
JNJ-1802 inhibits the replication of other flaviviruses West Nile Virus (WNV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV)), with mean EC50 values ranging from 0.25  µM to 1.1  µM, which is > 4,000‑fold higher than the EC50 value of JNJ-1802 for DENV‑2/16681 (IC50=0.059 nM).
JNJ-1802 shows antiviral activity and limited cellular toxicity in DENV-infected Vero, C6/36, Huh-7 and THP-1/DC-SIGN cells.
JNJ-1802 prevents de novo formation of NS3-NS4B complexes but does not disrupt established ones.
JNJ-1802 (0.2-6 mg per kg per day) exhibits a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes.
JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates.