Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors.
J Agric Food Chem
; 64(29): 5941-50, 2016 Jul 27.
Article
in En
| MEDLINE
| ID: mdl-27355875
ABSTRACT
Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with Q(2) = 0. 64, R(2)ncv = 0.93, R(2)pred = 0.80 and Q(2) = 0. 65, R(2)ncv = 0.98, R(2)pred = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Benzimidazoles
/
Pestivirus
/
Diarrhea
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Agric Food Chem
Year:
2016
Document type:
Article
Affiliation country:
China