Synergistic experimental/computational studies on arylazoenamine derivatives that target the bovine viral diarrhea virus RNA-dependent RNA polymerase

Bioorganic & Medicinal Chemistry
Gabriele GilibertiSabrina Pricl

Abstract

Starting from a series of arylazoenamine derivatives, shown to be selectively and potently active against the bovine viral diarrhea virus (BVDV), we developed a hierarchical combined experimental/molecular modeling strategy to explore the drug leads for the BVDV RNA-dependent RNA polymerase. Accordingly, BVDV mutants resistant to lead compounds in our series were isolated, and the mutant residues on the viral molecular target, the RNA-dependent RNA polymerase, were identified. Docking procedures upon previously identified pharmacophoric constraints and actual mutational data were carried out, and the binding affinity of all active compounds for the RdRp was estimated. Given the excellent agreement between in silico and in vitro data, this procedure is currently being employed in the design a new series of more selective and potent BVDV inhibitors.

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Citations

Feb 13, 2013·Chemical Biology & Drug Design·Marialaura AmadioSimona Collina
Jul 14, 2016·Journal of Chemical Information and Modeling·Kyrylo KlimenkoAlexandre Varnek
Dec 21, 2011·Antiviral Chemistry & Chemotherapy·Benjamin W NewcomerM Daniel Givens
Jan 12, 2021·Frontiers in Chemistry·Gabriela A FernándezLucia V Cavallaro
Jul 12, 2011·European Journal of Medicinal Chemistry·Antonio CartaSabrina Pricl

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