Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Molecular Modeling of Small Molecules as BVDV RNA-Dependent RNA Polymerase Allosteric Inhibitors

  • Chai, Han-Ha (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Lim, Dajeong (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Chai, Hee-Yeoul (Division of Biosafety Evaluation and Control, Korea National Institute of Health) ;
  • Jung, Eunkyoung (Insilicotech Co. Ltd.)
  • Received : 2012.10.09
  • Accepted : 2012.12.18
  • Published : 2013.03.20
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Abstract

Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.

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