Abstract
The influenza (“flu”) type-A 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 noble-metal nanoparticle conjugates of FluPep to enhance its antiviral activity and to determine their potential as a delivery platform for FluPep. FluPep ligand is FluPep extended at its N-terminus with the sequence CVVVTAAA, to allow for its incorporation into a mixed-matrix ligand shell of a peptidol and an alkanethiol ethylene glycol consisting of 70% CVVVTol and 30% HS(CH2)11(OC2H4)4OH (mol/mol). Gold and silver nanoparticles (ca. 10 nm diameter) with up to 5% (mol/mol) FluPep ligand remained as stable as the control of mixed-matrix-passivated nanoparticles in a variety of tests, including ligand exchange with dithiothreitol. The free FluPep ligand peptide 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). Nanoparticles functionalised with FluPep ligand showed enhanced antiviral activity compared to the free peptides. The IC50 value of the FluPep-functionalised nanoparticles decreased as the grafting density of FluPep ligand increased from 0.03% to 5% (both mol/mol), with IC50 values down to about 10% of that of the corresponding free peptide. 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 antimicrobial inhibitors, capable of targeting both influenza and bacterial co-infections.
Highlights
The influenza (“flu”) type-A virus is a major health concern for humans and livestock animals
The results demonstrate that the nanoparticle–FluPep ligand conjugates reduce the infectivity of influenza virus with greater antiviral activity than the free peptide, making this a viable tool for the development of a peptide formulation that efficiently combats seasonal, pandemic, and zoonotic influenza infections
The mixed-matrix ligand shell of 70:30 peptidol and alkanethiol ethylene glycol assembled on gold nanoparticles has a well-characterised stability with respect to ligand exchange and non-specific binding [26,27], but the effect of incorporating the FluPep amino acid sequence at the C-terminus of the CVVVT matrix sequence was unknown
Summary
The influenza (“flu”) type-A virus is a major health concern for humans and livestock animals. We have synthesized gold and silver nanoparticles functionalised with FluPep and analysed the anti-influenza activity of the nanoparticle–FluPep ligand conjugates. The incorporation of up to 5% (mol/mol) FluPep ligand in the ligand mixture did not reduce the stability of the gold nanoparticles with respect to ligand exchange and such nanoparticles could be used in cell culture medium.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
