title: Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling Pathways.
abstract: As the therapeutic agent for antiviral applications, 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 a possibility to be employed as a biomedical intervention. 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 for MDCK cells by controlled-potential electrolysis (CPE), MTT, and transmission electron microscopy (TEM). Furthermore, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) and then prevented the attachment of the H1N1 influenza virus to host cells. The investigations of the mechanism revealed that Ag@OTV could block H1N1 from infecting MDCK cells and prevent DNA fragmentation, chromatin condensation, and the activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species (ROS) by the H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticle based codelivery of oseltamivir inhibits the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1.
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Yinghua
authors: Y
authors: Li
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Zhengfang
authors: Z
authors: Lin
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Mingqi
authors: M
authors: Zhao
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Tiantian
authors: T
authors: Xu
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Changbing
authors: C
authors: Wang
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Liang
authors: L
authors: Hua
authors: State Key Laboratory of Virology, Chinese Academy of Sciences , Wuhan, P.R. China.
authors: Hanzhong
authors: H
authors: Wang
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Huimin
authors: H
authors: Xia
authors: Center Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, P.R. China.
authors: Bing
authors: B
authors: Zhu
mesh_terms: D000818:Animals; D000998:Antiviral Agents; D004285:Dogs; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D053768:Metal Nanoparticles; D053139:Oseltamivir; D017382:Reactive Oxygen Species; D012834:Silver
chemical_list: D000998:Antiviral Agents; D017382:Reactive Oxygen Species; D053139:Oseltamivir; D012834:Silver
keywords: apoptosis; influenza virus; neuraminidase; oseltamivir; silver nanoparticles