SAR Analysis of Novel Coxsackie virus A9 Capsid Binders

Enterovirus
infections are common in humans, yet there are no approved
antiviral treatments. In this study we concentrated on inhibition
of one of the Enterovirus B (EV-B), namely Coxsackievirus
A9 (CVA9), using a combination of medicinal chemistry, virus inhibition
assays, structure determination from cryogenic electron microscopy
and molecular modeling, to determine the structure activity relationships
for a promising class of novel N-phenylbenzylamines.
Of the new 29 compounds synthesized, 10 had half maximal effective
concentration (EC50) values between 0.64–10.46 μM,
and of these, 7 had 50% cytotoxicity concentration (CC50) values higher than 200 μM. In addition, this new series of
compounds showed promising physicochemical properties and act through
capsid stabilization, preventing capsid expansion and subsequent release
of the genome.