Molecular modelling studies on adamantane-based Ebola virus GP-1 inhibitors using docking, pharmacophore and 3D-QSAR

SAR and QSAR in Environmental Research
S N Mali, H K Chaudhari

Abstract

The pathogenic Ebola virus (EBOV) causes a potential health risk and global spread. To date, few drugs are available for the treatment of Ebola virus disease (EVD) that allow researchers to use computational methods for designing potential drugs. The developed PHASE-based common six-point pharmacophore hypothesis (AADHPR_1) showed the necessity of two hydrogen bond acceptor features, one hydrogen bond donor feature, one hydrophobic group feature, one positively ionizable and one aromatic ring feature for further designing. We developed best 3D-QSAR models with high regression coefficients for the training (r2>0.82) and test (Q2>0.5) sets for both atoms-based and field-based 3D-QSAR models. The molecule 1A-4 (docking score = -4.711 kcal/mol) was obtained as best docked (SP mode) on Ebola virus envelope glycoprotein (PDB ID-3CSY) as compared with the standards oseltamivir (docking score = -4.39 kcal/mol) and zanamivir (docking score = -3.392 kcal/mol). The obtained ZINC hit ZINC58935541 showed a good docking score of -4.892 kcal/mol. The ZINC58935541 molecule also showed a strong binding affinity towards the receptor cavity of Ebola virus envelope glycoprotein when simulated for 1.2 ns. The good QikProp parameters reflect the fac...Continue Reading

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Citations

Mar 20, 2020·Combinatorial Chemistry & High Throughput Screening·Marcel L AlmeidaMarina G R Pitta
May 21, 2019·Journal of Biomolecular Structure & Dynamics·Virendra R MishraNagaiyan Sekar
Jan 14, 2020·Journal of Biomolecular Structure & Dynamics·Muthumanickam SankarBoomi Pandi
Aug 24, 2019·Current Computer-aided Drug Design·Bhagwat S JadhavMustapha C Mandewale
Sep 3, 2019·Current Computer-aided Drug Design·Devidas G AnuseSuraj N Mali
Oct 28, 2019·Current Computer-aided Drug Design·Vijay J DesaleRamesh S Yamgar

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Software Mentioned

Epik
SwissTarget prediction
Maestro
SwissSimilarity
admetSAR
LigPrep
QikProp
MMGBSA
PHASE
Prime MMGBSA

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