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SAR Analysis of Novel Coxsackie virus A9 Capsid Binders.

Authors :
Tammaro C
Plavec Z
Myllymäki L
Mitchell C
Consalvi S
Biava M
Ciogli A
Domanska A
Leppilampi V
Buckner C
Manetto S
Sciò P
Coluccia A
Laajala M
Dondio GM
Bigogno C
Marjomäki V
Butcher SJ
Poce G
Source :
Journal of medicinal chemistry [J Med Chem] 2024 Oct 10; Vol. 67 (19), pp. 17144-17161. Date of Electronic Publication: 2024 Sep 18.
Publication Year :
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 (EC <subscript>50</subscript> ) values between 0.64-10.46 μM, and of these, 7 had 50% cytotoxicity concentration (CC <subscript>50</subscript> ) 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.

Details

Language :
English
ISSN :
1520-4804
Volume :
67
Issue :
19
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
39292620
Full Text :
https://doi.org/10.1021/acs.jmedchem.4c00701