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Enhanced inhibition of influenza virus infection by peptide-noble metal nanoparticle conjugates

Zaid K. Alghrair, View ORCID ProfileDavid G. Fernig, View ORCID ProfileBahram Ebrahimi
doi: https://doi.org/10.1101/324939
Zaid K. Alghrair
1Departments of Biochemistry Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, U.K
2Departments of Functional and Comparative Genomics Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, U.K
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David G. Fernig
1Departments of Biochemistry Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, U.K
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Bahram Ebrahimi
2Departments of Functional and Comparative Genomics Institute of Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, U.K
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Abstract

Influenza virus is a major medical and veterinary health concern and causes global pandemics. The peptide ‘FluPep’ is an established inhibitor of influenza virus infectivity in model systems. We have explored the potential for FluPep functionalised noble metal nanoparticle to enhance the antiviral activity of the peptide Flupep and determined their potential for the delivery of FluPep. The FluPep ligand designed here is FluPep extended at its N-terminus with the sequence CVVVTAAA-, to allow its incorporation into a mix matrix ligand shell of a peptidol and an alkanethiol ethyleneglycol comprising 70% H-CVVVTol and 30% HS(CH2)11(ethyleneglycol)4 (both mole/mole). Gold and silver nanoparticles (~10 nm diameter) prepared with up to 5% (mole/mole) FluPep ligand contained in the mixture of mix-matrix peptide ligands remained as stable as the control mix-matrix coated nanoparticles against ligand exchange with dithiothreitol. FluPep ligand was found to inhibit viral plaque formation in canine MDCK cells (IC50 2.1 nM), but was less potent than FluPep itself (IC50 140 pM). FluPep ligand functonalised nanoparticles retained antiviral activity in the plaque assay. Moreover, at low grafting densities (where nanoparticles incorporate ~1 FluPep ligand, the antiviral potency in terms of FluPep ligand concentration was enhanced significantly for gold and silver nanoparticles (IC50 ~8-fold and ~3-fold lower, respectively). At higher grafting density the potency relative to free FluPep ligand concentration decreased. The data demonstrate that conjugation of FluPep to gold and silver nanoparticles enhances its antiviral potency; the antimicrobial activity of silver ions may enable the design of even more potent anti-microbial inhibitors.

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Posted May 17, 2018.
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Enhanced inhibition of influenza virus infection by peptide-noble metal nanoparticle conjugates
Zaid K. Alghrair, David G. Fernig, Bahram Ebrahimi
bioRxiv 324939; doi: https://doi.org/10.1101/324939
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Enhanced inhibition of influenza virus infection by peptide-noble metal nanoparticle conjugates
Zaid K. Alghrair, David G. Fernig, Bahram Ebrahimi
bioRxiv 324939; doi: https://doi.org/10.1101/324939

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