Enhanced inhibition of influenza virus infection by peptide-noble-metal nanoparticle conjugates.
Zaid K AlghrairDavid G FernigBahram EbrahimiPublished in: Beilstein journal of nanotechnology (2019)
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.
Keyphrases
- silver nanoparticles
- healthcare
- cancer therapy
- mental health
- human health
- gold nanoparticles
- machine learning
- drug delivery
- staphylococcus aureus
- induced apoptosis
- air pollution
- risk assessment
- cell cycle arrest
- artificial intelligence
- cell death
- endoplasmic reticulum stress
- room temperature
- signaling pathway
- health promotion
- data analysis