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

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(CH 2 ) 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 (IC 50 2.1 nM), but was less potent than FluPep itself (IC 50 140 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 (IC 50 ~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.

Nanotechnology-based antiviral therapeutics

“…Emileh et al have reported gold nanoparticle–peptide triazole conjugates to be active against HIV-1 by disrupting the interactions between host receptor proteins and trimeric envelope spike glycoprotein of virus [ 155 ]. Recently, Alghrair et al functionalized silver and gold nanoparticles with an antiviral peptide FluPep and reported increased antiviral potency against influenza A virus [ 156 ].…”

Nanoparticle-Based Strategies to Combat COVID-19

“…Alghrair et al reported that AgNPs and AuNPs functionalized with FluPep, a peptide that can effectively inhibit influenza A viruses (IAVs), showed greater antiviral activity than free FluPep. 94 Haag and co-workers used electron microscopy imaging to visually show that AuNPs functionalized with sialic-acid-terminated glycerol dendrons specifically targeted the viral HA protein to effectively inhibit viral proliferation. 55 Moreover, various NPs, such as oseltamivir-functionalized AgNPs, 63 AgNP/chitosan composites, 95 zanamivir-functionalized AgNPs, 64 zanamivir-functionalized SeNPs (through the p38 and JNK signaling pathways), 67 amantadine-functionalized SeNPs (through the ROS-mediated AKT signaling pathways), 68 ribavirin-functionalized SeNPs (via the caspase-3 apoptotic pathway), 69 oseltamivir-functionalized SeNPs, 70 PEGylated-ZnO NPs, 71 and anionic AuNPs, 56 have also been fabricated and investigated for inhibitory effects on and biocompatibility with H1N1, a current seasonal virus that caused two deadly global pandemics in 1918 and 2009.…”

Metal Nanoparticles: a Promising Treatment for Viral and Arboviral Infections

“…"FluPep" is an established peptide inhibitor of influenza type-A virus; however, silver and gold peptide (FluPep) NPs were synthesized and tested for enhanced antiviral activity [146]. Silver and gold NPs functionalized with FluPep ligand (0.03%) showed inhibition (50%) against the influenza A virus strain at concentrations of 0.14 nM and 0.073 nM, respectively.…”