SAR Analysis\nof\nNovel Coxsackie virus A9 Capsid Binders

Enterovirus\ninfections are common in humans, yet there are no approved\nantiviral treatments. In this study we concentrated on inhibition\nof one of the <i>Enterovirus B</i> (EV-B), namely Coxsackievirus\nA9 (CVA9), using a combination of medicinal chemistry, virus inhibition\nassays, structure determination from cryogenic electron microscopy\nand molecular modeling, to determine the structure activity relationships\nfor a promising class of novel <i>N</i>-phenylbenzylamines.\nOf the new 29 compounds synthesized, 10 had half maximal effective\nconcentration (EC<sub>50</sub>) values between 0.64–10.46 μM,\nand of these, 7 had 50% cytotoxicity concentration (CC<sub>50</sub>) values higher than 200 μM. In addition, this new series of\ncompounds showed promising physicochemical properties and act through\ncapsid stabilization, preventing capsid expansion and subsequent release\nof the genome.