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Combinatorial Chemistry & High Throughput Screening

Author(s): Hina Khalid and Usman Ali Ashfaq*

DOI: 10.2174/1386207323666201228160224

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Molecular Docking and Pharmacoinformatics Studies Reveal Potential Phytochemicals Against HCV NS5B Polymerase

Page: [335 - 346] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Background: Hepatitis C Virus (HCV) is one of the serious health issues affecting onethird of the world’s population. The high variations of the HCV genome are ascribed to quick replication by NS5B polymerase and are thus the most attractive target for developing anti-HCV agents.

Objective: The current study aimed to discover novel phytochemicals that harbor the potential of NS5B polymerase inhibition.

Methods: In this computational study, a molecular docking approach was used to screen phytochemicals with the best binding and spatial affinity with NS5B at the Palm I region. The topranked compounds were then subjected to an in-silico pharmacokinetic and toxicological study.

Results: The virtual screening provided seven ‘hit compounds’ including Betanin, 3,5'- dihydroxythalifaboramine, Diarctigenin, 6'-desmethylthalifaboramine, Cephalotaxine, 5alpha-O- (3'-dimethylamino-3'-phenylpropionyl) taxinine M and IsoTetrandrine with minimum binding score compared to the reference drug, sofosbuvir (−14.7 kcal/mol). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and thorough toxicological analysis revealed a favorable safety profile of these compounds.

Conclusion: The study demonstrates the identified phytochemicals. These may serve as potential antiviral compounds that can provide an alternative approach for amelioration of HCV.

Keywords: Hepatitis C, NS5B inhibitors, antiviral, molecular docking, phytochemicals, mammalian host cells.

Graphical Abstract

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