Background: Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations.
Main body: In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold-thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA.
Conclusion: We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.
Keywords: Disulfide bond; Influenza A virus; Membrane fusion; Porous gold nanoparticle; Virus inactivation.