Molecular docking based screening of compounds against VP40 from Ebola virus

Abstract

Ebola virus causes severe and often fatal hemorrhagic fevers in humans. The 2014 Ebola epidemic affected multiple countries. The virus matrix protein (VP40) plays a central role in virus assembly and budding. Since there is no FDA-approved vaccine or medicine against Ebola viral infection, discovering new compounds with different binding patterns against it is required. Therefore, we aim to identify small molecules that target the Arg 134 RNA binding and active site of VP40 protein. 1800 molecules were retrieved from PubChem compound database based on Structure Similarity and Conformers of pyrimidine-2, 4-dione. Molecular docking approach using Lamarckian Genetic Algorithm was carried out to find the potent inhibitors for VP40 based on calculated ligand-protein pairwise interaction energies. The grid maps representing the protein were calculated using auto grid and grid size was set to 60*60*60 points with grid spacing of 0.375 Ǻ. Ten independent docking runs were carried out for each ligand and results were clustered according to the 1.0 Ǻ RMSD criteria. The post-docking analysis showed that binding energies ranged from -8.87 to 0.6 Kcal/mol. We report 7 molecules, which showed promising ADMET results, LD-50, as well as H-bond interaction in the binding pocket. The small molecules discovered could act as potential inhibitors for VP40 and could interfere with virus assembly and budding process.

Advances in Designing and Developing Vaccines, Drugs, and Therapies to Counter Ebola Virus

“…Insertional mutagenesis, a high-throughput method to identify genes responsible for virus replication, can be used to develop drug candidates ( 132 ). Molecular docking experiments with EBOV GPs can be used for drug designing and the development of therapeutics ( 133 , 134 ). Novel flexible nucleosides called fleximers were found to be effective against recombinant EBOV in Huh7 cells ( 135 ).…”

Identification of Potent Inhibitors against NS3 Protease of West Nile Virus using in Silico Approaches

“…In additions to using them for docking, the atomic affinity grids can be visualized [11]. 2) Autodock Tool: AutoDock Tool is the free GUI for AutoDock program .We can use it to set up, run and analyse AutoDock dockings and isocontour AutoGrid affinity maps, as well as compute molecular surfaces, display secondary structure ribbons, count hydrogen-bonds, and do many more useful things [12]. 3) Cygwin: Cygwin is a collection of free software tools originally developed by Cygnus Solutions to permit various versions of Microsoft Windows to act similar to a Unix system.…”

“…To avoid this failure at the development a set of in vitro ADME/Tox screens has been implemented with the target of discarding compounds in the discovery phase that are likely to fail further down the line [17]. The preADMET server calculates parameters such as human intestinal absorption, cellular permeability of Caco-2 in vitro, cell permeability, skin permeability, plasma protein binding, and blood -brain barrier penetration, mutagenicity and carcinogenicity [12] [18].…”

Virtual Screening and ADME/Tox Study of Inhibitors against Ebola Virus Matrix Protein VP40

“…CASTp server uses the weighted Delaunay triangulation and the alpha complex for shape measurements [9]. This software allows the identification and measurements of surface accessible pockets as well as interior inaccessible cavities of protein structures and other molecules [11].…”

“…VP40 is dynamic not just in the lipid bilayer amid the gathering procedure yet in addition assumes an imperative part either in viral or have cell RNA digestion amid its replication [7]. Cterminal area of VP40 is required for layer affiliation [9].…”