In silico identification and study of potential anti-mosquito juvenile hormone binding protein (MJHBP) compounds as candidates for dengue virus - Vector insecticides

Abstract

Dengue has become a huge global health burden. It is currently recognized as the most rapidly spreading mosquito-borne viral disease. Yet, there are currently no licensed vaccines or specific therapeutics to manage the virus, thus, scaling up vector control approaches is important in controlling this viral spread. This study aimed to identify and study in silico , potential anti-mosquito compounds targeting Juvenile hormone (JH) mediated pathways via the Mosquito Juvenile Hormone Binding Protein (MJHBP). The study was implemented using series of computational methods. The query compounds included pyrethroids and those derived from ZINC and ANPDB databases using a simple pharmacophore model in Molecular Operating Environment (MOE). Molecular docking of selected compounds’ library was implemented in MOE. The resultant high-score compounds were further validated by molecular dynamics simulation via Maestro 12.3 module and the respective Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) binding energies computed. The study identified compounds-pyrethroids, natural and synthetic - with high docking energy scores (ranging from 10.91–12.34 kcal/mol). On further analysis of the high-ranking (in terms of docking scores) compounds using MD simulation, the compounds - Ekeberin D4, Maesanin, Silafluofen and ZINC16919139- revealed very low binding energies (−122.99, −72.91 -104.50 and,-74.94 kcal/mol respectively), fairly stable complex and interesting interaction with JH-binding site amino acid residues on MJHBP. Further studies can explore these compounds in vitro/in vivo in the search for more efficient mosquito vector control.

In Silico Studies on Zinc Oxide Based Nanostructured Oil Carriers with Seed Extracts of Nigella sativa and Pimpinella anisum as Potential Inhibitors of 3CL Protease of SARS-CoV-2

“…The stability of the protein-ligand complex is primarily due to the non-covalent interactions (hydrophobic contacts, hydrogen bonds, water bridges, salt bridges) between proteins and ligands, which in turn significantly impact the resulting binding energy [51]. In the present study, the MD simulation showed that dithymoquinone, δ-hederin, and oleuropein exhibited maximum water bridges, along with hydrogen bonding and hydrophobic interactions, which reflected a stable ligand-protein interaction.…”

“…All the optimized compounds used in the present study did show minor ranges of initial/later fluctuations but were equilibrated over a long range, indicating stability. Taken together, the four compound-protein complexes seem to be fairly stable as the RMSD values were observed to be far less than 3.0 Å, which is considered stable [51]. The high RMSF value shows more flexibility, whereas low RMSF value shows limited movements.…”

“…The standalone, offline software used was the Molecular Operating Environment, 2015 version (Chemical Computing Group, Montreal, QC, Canada) and the Discovery Studio 2019 Client Full Package (Biovia, San Diego, CA, USA). The molecular docking study and the molecular dynamic simulation was performed in accordance with the methods used in a previous study by Ononamadu et al [51].…”

Searching of Novel Herbicides for Paddy Field Weed Management—A Case Study with Acetyl-CoA Carboxylase

“…The ligand interaction diagram (LID) and docked ACCase-FPPE and ACCase-sinigrin complexes are shown in Figures 3 and 4, respectively. Despite the number of binding interactions, hydrogen bonding is one of the important non-covalent interactions in stabilizing the protein-ligand complex [68]. Consistently, it is apparent from the figure that the amino acids THR318 and ASN373 are the key residues involved in hydrogen bond interaction in both FPPE and the sinigrin complex (Figure 3a).…”

In-silico investigation of phenolic compounds from leaves of Phillyrea angustifolia L. as a potential inhibitor against the SARS-CoV-2 main protease (Mpro PDB ID:5R83) using a virtual screening method

“…Out of the four selected phenolic compounds, Oleuropein aglycone displayed the lowest total binding free energy. Among all the interactions, the contribution of the Coulomb energy (Coulomb), and the Van der Waals energy were more remarkable than other items of binding free energy ( Table 3 ) [41] .…”