SAR Analysis of Novel Coxsackie virus A9 Capsid Binders.
Chiara TammaroZlatka PlavecLaura MyllymäkiCristopher MitchellSara ConsalviMariangela BiavaAlessia CiogliAušra DomanskaValtteri LeppilampiCienna BucknerSimone ManettoPietro SciòAntonio ColucciaMira LaajalaGiulio M DondioChiara BigognoVarpu S MarjomakiSarah J ButcherGiovanna PocePublished in: Journal of medicinal chemistry (2024)
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 (EC 50 ) values between 0.64-10.46 μM, and of these, 7 had 50% cytotoxicity concentration (CC 50 ) 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.