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Molecular Optimization, Docking and Dynamic Simulation Study of Selective Natural Aromatic Components to Block E2-CD81 Complex Formation in Predating Protease Inhibitor Resistant HCV Influx
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| Author:
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, MD.ARMAN SHARIF, MD.SADDAM HOSSEN, MAHDI MUBIN SHAIKAT, FARHAN MASHUK HAIDARY, TANZILA ISMAIL EMA, DIPTA DEY, PARAG KUMAR PAUL, SALAUDDIN AL AZAD, MOHAMMAD FAYSAL AL MAZID, MD.NASIR UDDIN BADAL
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| Abstract:
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The comprehensive research aimed to figure out selective novel aromatic phytochemical ligands to impede Hepatitis C Virus infection through aborting CD81-E2 complex formation in the liver surface prior to E2 virulence factor influx. A library of fifty aromatic pharmacophore ligands was constructed, from where six best performing were selected depending on their absorption, distribution, metabolism, excretion and toxicity status as well as quantitative structure-activity relationship properties. According to the molecular optimization, docking and dynamic simulation features for over 50 nanosecond, the order of target specificity towards CD81 receptor is predicted as Alpha and Beta Amyrin>Delta Amyrin>Benzyl Carbamate>Benzoic acid>Benzyl Mercaptan. With the value of (-5.8 KJ/mol) binding affinity, Alpha and Beta Amyrin referring the most stable ligands among the other ligands. The RMSD values of protein-ligand complexes ranged between 0.1~2.6 Å, assessed according to their structural conformation and stable binding position. The peak-fluctuation-regions of RMSF ranged from 0.1 to 4.2 Å, resulted with effective ligand-receptor interactions. Similarly, radius of gyration, molecular surface area and solvent accessible surface area revealed the pharmacokinetic potentiality of the ligands as target specific towards CD81 receptor macromolecule. Finally, the polar surface area confirmed the blood brain barrier penetration efficacy and therapeutic accuracy of Benzoic Acid, Benzyl Mercaptan, Alpha and Beta Amyrins against HCV infection, because of having the polar area below 90Å. To estimate the best therapeutic efficacies of the designed aromatic ligands, an in silico and in vivo integrative research is to be conducted prior to approaching any clinical trial as Hepatitis C Virus drugs.
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| Keyword:
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hepatitis C virus, protease inhibitor resistant, aromatic natural components, CD81-E2 complex formation, molecular optimization and docking, molecular dynamic simulation, targeted antiviral drug design
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| EOI:
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| DOI:
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https://doi.org/10.31838/ijpr/2021.13.02.408
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| Download:
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