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 mu M, and of these, 7 had 50% cytotoxicity concentration (CC50) values higher than 200 mu M. 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.

SAR Analysis of Novel Coxsackie virus A9 Capsid Binders / Tammaro, Chiara; Plavec, Zlatka; Myllymäki, Laura; Mitchell, Cristopher; Consalvi, Sara; Biava, Mariangela; Ciogli, Alessia; Domanska, Aušra; Leppilampi, Valtteri; Buckner, Cienna; Manetto, Simone; Sciò, Pietro; Coluccia, Antonio; Laajala, Mira; Dondio, Giulio M; Bigogno, Chiara; Marjomäki, Varpu; Butcher, Sarah J; Poce, Giovanna. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2024). [10.1021/acs.jmedchem.4c00701]

SAR Analysis of Novel Coxsackie virus A9 Capsid Binders

Tammaro, Chiara
Primo
Membro del Collaboration Group
;
Consalvi, Sara
Membro del Collaboration Group
;
Biava, Mariangela
Membro del Collaboration Group
;
Ciogli, Alessia
Membro del Collaboration Group
;
Manetto, Simone;Coluccia, Antonio;Poce, Giovanna
Ultimo
Membro del Collaboration Group
2024

Abstract

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 mu M, and of these, 7 had 50% cytotoxicity concentration (CC50) values higher than 200 mu M. 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.
2024
antivirals; drug design; Coxsackievirus A9; cryoEM; hydrophobic pocket; genome release prevention
01 Pubblicazione su rivista::01a Articolo in rivista
SAR Analysis of Novel Coxsackie virus A9 Capsid Binders / Tammaro, Chiara; Plavec, Zlatka; Myllymäki, Laura; Mitchell, Cristopher; Consalvi, Sara; Biava, Mariangela; Ciogli, Alessia; Domanska, Aušra; Leppilampi, Valtteri; Buckner, Cienna; Manetto, Simone; Sciò, Pietro; Coluccia, Antonio; Laajala, Mira; Dondio, Giulio M; Bigogno, Chiara; Marjomäki, Varpu; Butcher, Sarah J; Poce, Giovanna. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - (2024). [10.1021/acs.jmedchem.4c00701]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1720626
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