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.

Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats

“…To uncover the synergistic effects of Ecdysterone-Paeonol on multiple targets in the treatment of radiation-induced oral mucositis, as well as to assess their mechanisms, a compound−target (C–T) network, as shown in Figure 5, was constructed using detailed information of the targets provided in Table 1. All of these results indicated that Ecdysterone-Paeonol affected multiple targets and showed a synergistic effect [18,19,20].…”

Mechanism Exploration of Arylpiperazine Derivatives Targeting the 5-HT2A Receptor by In Silico Methods

“…Generally, a Q 2 value above 0.5 is regarded as a sign of admissible internal predictive ability. Besides, the high R 2 ncv and F but low SEE values are also expected for a reliable QSAR model [ 19 ]. In the present work, by means of PLS statistical analysis, the resultant CoMFA model obtained by using both the steric and electrostatic field descriptors is unsatisfied with Q 2 value of 0.496, revealing a relatively poor internal predictability.…”

“…With the rapid development of computer technology, chemical biology, and molecular biology, computer simulation technology plays an prominent role in the growth of new agents [ 16 , 17 ]. As known to all, computer-aided drug design (CADD) can greatly raise the efficiency of developing and designing novel drugs, and thus has been used more and more diffusely in present pharmaceutical industry [ 18 , 19 ]. In fact, CADD approaches, like especially the 3D-QSAR, molecular docking, molecular dynamics (MD), homology modeling and pharmacophore mapping techniques, have been vastly conducted in the optimization and development of inhibitors [ 20 , 21 ], in which 3D-QSAR modeling has proven its efficiency in exploring the pharmacological properties of the studied molecules in modern drug discovery [ 22 , 23 ].…”

Recent Developments and Applications of the MMPBSA Method

“…Influenza was also an important research topic in antiviral compounds, with targets such as neuraminidase protein (Wang and Chen, 2014 ; Tran et al, 2015 ; Chintakrindi et al, 2016 ; Yang et al, 2016 ), non-structural proteins (Ai et al, 2014 ), H7N9 neuraminidase (Phanich et al, 2016 ), and the M2 proton channel (Homeyer et al, 2016 ). Other antiviral targets were also examined, such as RNA-dependent RNA polymerase (Yu et al, 2014 ; Wang J. H. et al, 2016 ), NS3/4A hepatitis C virus protease (Xue et al, 2014 ; Fu and Wei, 2015 ; Meeprasert et al, 2016 ), human furin (Omotuyi, 2015 ), and the capsomere of virus-like particles (Li Y. Y. et al, 2014 ). The method was additionally applied to the identification of novel protease targets for antiviral compounds (Pethe et al, 2017 ).…”