JNJ-7184 is a potent, selective and non-nucleoside inhibitor of RSV-Large (L) polymerase, displays potent inhibition of both RSV-A and -B strains with EC50 of 13 and 72 nM in vitro.
JNJ-7184 targets the connector domain of RSV L polymerase.
JNJ-7184 blocks early elongation of vRNA products and partly 1st dinucleotide formation.
JNJ-7184 interacts with the connector domain (CD) located between the PRNTase and MTase domains of RSV-L.
JNJ-7184 is selective for RSV, showsweak activity against VSV, DENV-2, HIV-1 and CMV (EC50 of 3.8-79 μM).
JNJ-7184 displays little to no detectable inhibition of human DNA polymerases α, β, and γ, human mitochondrial RNA polymerase, and human RNA polymerase II (EC50 >40 uM).
JNJ-7184 inhibits RSV RNA-dependent RNA polymerase (RdRp) activity in a primer extension assay based on the purified L and P proteins (EC50=21 nM).
JNJ-7184 (1, 4 and 16 mg/kg) is highly efficacious in vivo in neonatal lambs.