Peptide-Functionalized Gold Nanoparticles are Potent Inhibitors of Respiratory Syncytial Virus (RSV) Infection

摘要

Human respiratory syncytial virus (RSV) is a major cause of severe upper and lower respiratory tract infections in infants, and in high-risk adults. Currently, there is no vaccine and the available therapeutic agents have limited efficacy. Gold Nanoparticles represent good therapeutic agents due their antibacterial and antiviral properties and an important strategy for efficient delivery of therapeutic agents to maximize therapeutic activity. In the present work, we investigated, in vitro, the potency enhancement of the antiviral activity by functionalization of gold nanoparticle with different anti-RSV peptides targeting the virus entry. Carboxylated Gold nanoparticles of 15 nm diameter size were conjugated with 1) a dendrimeric Heparan Sulfate-Binding Peptide (SB105-A10); and 2) with a small dendrimer-like peptide (T118). SB105-A10 and T118 are known RSV entry inhibitors by competing for binding to cell surface HSPGs and via interactions with RSV fusion protein, respectively. No significant increase (less than 10%) in cell cytotoxicity was observed with nanoparticle concentration up to 100 μg/mL. NPs were allowed to interact respectively with viral particles before infecting the cells as well as interacted with RSV-infected cells. At 30 μg/mL (～ 1.5 nM) concentration, they showed high inhibitory activity of RSV infection and infectivity (＞60% inhibition and ≥3-fold reduction of the virus titer). However, when NPs were added in RSV-infected cells, they exhibited less inhibitory activity of RSV (＜50% inhibition). Furthermore, the functionalization of Au-NPs with T118 showed an increase of the antiviral activity as compared to non-functionalized nanoparticles. Our results suggest that the functionalization of gold nanoparticles may be effective strategy for the development of broad-spectrum anti-RSV agents inhibiting RSV infection as well as preventing the spread of the virus among already infected cells.