A Novel Chimeric Anti-HCV Peptide Derived from Camel Lactoferrin and Molecular Level Insight on Its Interaction with E2

Abstract

In the present study, a novel chimeric peptide was derived from camel lactoferrin designed with a considerable anti-HCV activity and its neutralization mechanism was predicted by molecular modelling tools. A novel anti-HCV peptide derived from camel lactoferrin (cLF36) was designed and expressed it recombinantly in HEK-293-T cells. Anti-viral activity of this peptide was evaluated against hepatitis C virus by Real-time PCR assay in vitro. Finally, to have a better insight into the mode of action of peptide on HCV entry inhibition, we examined the interaction of cLF36 with envelope glycoprotein E2 by molecular dynamic simulation. This chimeric peptide had significant inhibitory effects on both HCV entry (44 µg/mL) and viral replication (88 µg/mL) under in vitro (p > 0.01). Moreover, cLF36 peptide was not toxic to HEK cells as a normal cell at twofold of its anti-viral concentrations for HCV entry and even at concentrations as high as 250 µg/mL exhibited minimal hemolysis (2.5%) against human RBCs (red blood cells). The results of in silico analysis showed that cLF36 interacted with β-sandwich and front layer of E2 protein as two potential CD81 binding sites. We generated and characterized a new camel lactoferrin derived HCV inhibitors. This peptide blocked HCV entry and also intracellular HCV replication in cell culture experiment.

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Acknowledgements

The authors would also like to express their gratitude to the Ferdowsi University of Mashhad for their support. The present study was funded by INFS (infs.gov.ir) of I.R.I with Grant No. 93,025,031.

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Correspondence to Mohammad Hadi Sekhavati.

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Approvals to conduct experimental protocols to study hemolysis on human red cells were approved by the Committee on Publication Ethics (COPE), where this work was done. Human red cells were from volunteer Mohammad Hadi Sekhavati, who signed the informed consent for this study and is also author of this report.

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Tahmoorespur, M., Azghandi, M., Javadmanesh, A. et al. A Novel Chimeric Anti-HCV Peptide Derived from Camel Lactoferrin and Molecular Level Insight on Its Interaction with E2. Int J Pept Res Ther 26, 1593–1605 (2020). https://doi.org/10.1007/s10989-019-09972-7

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Keywords

  • Anti-HCV peptide
  • Camel
  • Lactoferrin
  • Envelope glycoprotein E2
  • Molecular dynamic simulation