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Letters in Drug Design & Discovery

Author(s): Varsha Dwivedi, Rakesh Kumar Gupta, Amita Gupta, Vijay K Chaudhary, Sanjay Gupta and Vandana Gupta*

DOI: 10.2174/1570180819666220124112150

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Repurposing Novel Antagonists for Targeting p7 Viroporin of HCV Using In Silico Approach

Page: [969 - 981] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: P7 viroporin in HCV is a cation-selective ion channel-forming protein, functional in the oligomeric form. It is considered to be a potential target for anti-HCV compounds due to its crucial role in viral entry, assembly, and release.

Methods: Conserved crucial residues present in HCV p7 protein were delineated from the available literature with a specific focus on the genotypes 3a and 1b prevalent in India. Using the Flex-X docking tool, a library of FDA-approved drugs was docked on the receptor sites prepared around crucial residues. In the present study, we proposed drug repurposing to target viroporin p7, which may help in the rapid development of effective anti-HCV therapies.

Results: With our approach of poly-pharmacology, a variety of drugs currently identified as antibiotics, antiparasitic, antiemetic, anti-retroviral, and anti-neoplastic were found to dock successfully on the p7 viroporin. Noteworthy among these are general-purpose cephalosporin antibiotics, leucal, phthalylsulfathiazole, and granisetron, which may be useful in acute HCV infection, and anti-neoplastic sorafenib and nilotinib, which may be valuable in advanced HCV-HCC cases.

Conclusion: This study could pave the way for quick repurposing of these compounds as anti-HCV therapeutics.

Keywords: Hepatitis C virus, viroporin, p7, drug-repurposing, in silico screening, polypharmacology.

Graphical Abstract

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