title: Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors.
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.
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Ministry of Education, Shihezi University , Shihezi 832002, China.|Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology , Dalian, Liaoning 116024, P. R. China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Ministry of Education, Shihezi University , Shihezi 832002, China.|Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology , Dalian, Liaoning 116024, P. R. China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Ministry of Education, Shihezi University , Shihezi 832002, China.|Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology , Dalian, Liaoning 116024, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Pharmacy School, Ministry of Education, Shihezi University , Shihezi 832002, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002418:Cattle Diseases / Q000821:virology; D003967:Diarrhea / Q000662:veterinary* / Q000821:virology; D015195:Drug Design; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010576:Pestivirus / Q000187:drug effects* / Q000502:physiology; D018182:Pestivirus Infections / Q000821:virology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles
keywords: 3D-QSAR; BVDV RdRp; MM-PBSA; docking; molecular dynamics