Porous gold nanoparticles for attenuating infectivity of influenza A virus

• Published in: Journal of nanobiotechnology Vol. 18; no. 1; pp. 54 - 11
• Main Authors: Kim, Jinyoung, Yeom, Minjoo, Lee, Taeksu, Kim, Hyun-Ouk, Na, Woonsung, Kang, Aram, Lim, Jong-Woo, Park, Geunseon, Park, Chaewon, Song, Daesub, Haam, Seungjoo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.03.2020; BioMed Central; BMC
• Subjects: Animals; Antiviral agents; Antiviral Agents - pharmacology; Avian influenza; Avian influenza viruses; Binding; Binding sites; Biocompatibility; Bonding strength; Cell viability; Chemical bonds; Cytotoxicity; Disulfide bond; Disulfide bonds; Dogs; Drug targeting; Drug therapy; Exo-a-sialidase; Gene mutation; Genes; Gold; Gold - pharmacology; Hemagglutinins; Infections; Infectivity; Influenza; Influenza A; Influenza A virus; Influenza A virus - drug effects; Influenza A virus - genetics; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H3N2 Subtype - drug effects; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H9N2 Subtype - drug effects; Influenza A Virus, H9N2 Subtype - genetics; Influenza research; Lectins; Madin Darby Canine Kidney Cells; Matrix protein; Membrane Fusion; Membranes; Metal Nanoparticles - chemistry; Microbial drug resistance; Morphology; Mutation; Nanoparticles; Pandemics; Polymerase chain reaction; Porosity; Porous gold nanoparticle; Povidone; Product development; Protein binding; Proteins; Ribonucleic acid; RNA; RNA viruses; RNA, Viral - analysis; RNA, Viral - genetics; Strains (organisms); Surface active agents; Surface science; Surfactants; Swine flu; Thiols; Time; Vaccines; Viral infections; Virus diseases; Virus inactivation; Virus Internalization; Viruses; South Korea; United States > US; Membrane fusion; Influenza A virus; Disulfide bond; Virus inactivation; Porous gold nanoparticle
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-020-00611-8

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. 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. 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.