Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an
Antiviral efficacy
dynamic simulation
molecular docking
principal component analysis
targeted drug designing
Journal
Journal of advanced veterinary and animal research
ISSN: 2311-7710
Titre abrégé: J Adv Vet Anim Res
Pays: Bangladesh
ID NLM: 101647585
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
07
10
2020
revised:
11
12
2020
accepted:
24
12
2020
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
17
4
2021
Statut:
epublish
Résumé
The comprehensive A library of 57 aromatic pharmacophore phytochemical ligands was prepared from where the top five ligands depending on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and quantitative structure-activity relationship (QSAR)-based pharmacokinetic properties were considered. The selected ligands were optimized for commencing molecular docking and dynamic simulation as a complex with the ACE2 receptor to compare their blocking efficacy with the control drug. The ligand-receptor complexes' accuracy in preventing the Spike (S) protein of SARS-CoV-2 penetration inside the host cells has been analyzed through hydrogen-hydrophobic bond interactions, principal component analysis (PCA), root mean square deviation (RMSD), root mean square fluctuation (RMSF), and B-Factor. Advanced ADMET and QSAR revealed Rhamnetin, Lactupicrin, Rhinacanthin D, Flemiflavanone D, and Exiguaflavanone A as the ligands of our interest to be compared with the control Cassiarin D. According to the molecular docking binding affinity to block ACE2 receptor, the efficiency mountings were Rhinacanthin D > Flemiflavanone D > Lactupicrin > Exiguaflavanone A > Rhamnetin. The binding affinity of the Cassiarin D-ACE2 complex was (-10.2 KJ/mol) found inferior to the Rhinacanthin D-ACE2 complex (-10.8 KJ/mol), referring to Rhinacanthin D as a more stable candidate to use as drugs. The RMSD values of protein-ligand complexes evaluated according to their structural conformation and stable binding pose ranged between 0.1~2.1 Å. The B-factor showed that very few loops were present in the protein structure. The RMSF peak fluctuation regions ranged 5-250, predicting efficient ligand-receptor interactions. The experiment sequentially measures all the parameters required in referring to any pharmacophore as a drug, considering which all aromatic components analyzed in the study can strongly be predicted as target-specific medication against the novel coronavirus 2019 infection.
Identifiants
pubmed: 33860009
doi: 10.5455/javar.2021.h481
pmc: PMC8043340
doi:
Types de publication
Journal Article
Langues
eng
Pagination
24-35Informations de copyright
Copyright: © Journal of Advanced Veterinary and Animal Research.
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interests.
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