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《2017新发传染病研究热点研讨会论文集》2017年
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Silver nanoparticles based co-delivery of Oseltamivir to inhibit the activity of H1N1 influenza virus through ROS-mediated signaling pathways

Yinghua Li  Zhengfang Lin  Bing Zhu  
【摘要】:As the therapeutic agent for antiviral, the clinical use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles(AgNPs) has attracted increasing attention in recent years and was possibility to be employed as biomedical interventions. Herein, we describe the synthesis of surface decoration of AgNPs by using oseltamivir(OTV) with antiviral properties and inhibition of drug resistance. Compared to silver and oseltamivir, oseltamivir modified AgNPs(Ag@OTV) have remarkable inhibition against H1N1 infection and less toxicity was found to MDCK cells by CPE, MTT and TEM. Furthermore, Ag@OTV inhibited the activity of neuraminidase(NA) and hemagglutinin(HA), and then prevented the attachment of H1N1 influenza virus to host cells. The mechanism investigations revealed that Ag@OTV could block H1N1 form infecting MDCK cells and prevent DNA fragmentation, chromatin condensation and activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species(ROS) by H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticles based co-delivery of oseltamivir inhibits the activity of H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1. Keywords: Oseltamivir; Silver nanoparticles; Influenza virus; Neuraminidase; Apoptosis.

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