Gold/Silver Hybrid Nanoparticles with Enduring Inhibition of Coronavirus Multiplication through Multisite Mechanisms

As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, Au@Ag nanorods (Au@AgNRs) were successfully synthesized by coating AuNRs with silver and were...

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Bibliographic Details
Published in:Bioconjugate chemistry 2020-11, Vol.31 (11), p.2553-2563
Main Authors: Du, Ting, Zhang, Jinyu, Li, Chunqiao, Song, Tao, Li, Ping, Liu, Jifeng, Du, Xinjun, Wang, Shuo
Format: Article
Language:English
Subjects:
Animals
Antiviral activity
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Antiviral Agents - toxicity
Biodiversity
Caspase-3
Cell proliferation
Chlorocebus aethiops
Coronaviridae
Coronaviruses
Diarrhea
Dose-Response Relationship, Drug
Epidemics
Gold
Gold - chemistry
Gold - pharmacology
Gold - toxicity
Infections
Membrane potential
Metal Nanoparticles - chemistry
Mitochondria
Multiplication
Nanoparticles
Nanorods
Nanotubes - chemistry
Porcine epidemic diarrhea virus - drug effects
Porcine epidemic diarrhea virus - physiology
Reactive oxygen species
Replication
RNA viruses
Silver
Silver - chemistry
Transmissible gastroenteritis
Vero Cells
Virus Replication - drug effects
Viruses
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Summary:As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, Au@Ag nanorods (Au@AgNRs) were successfully synthesized by coating AuNRs with silver and were shown for the first time to have activity against the replication of porcine epidemic diarrhea virus (PEDV). Viral titer analysis demonstrated that Au@AgNRs could inhibit PEDV infection by 4 orders of magnitude at 12 h post-infection, which was verified by viral protein expression analysis. The potential mechanism of action showed that Au@AgNRs could inhibit the entry of PEDV and decrease the mitochondrial membrane potential and caspase-3 activity. Additionally, we demonstrated that a large amount of virus proliferation can cause the generation of reactive oxygen species in cells, and the released Ag+ and exposed AuNRs by Au@AgNRs after the stimulation of reactive oxygen species has superior antiviral activity to ensure long-term inhibition of the PEDV replication cycle. The integrated results support that Au@AgNRs can serve as a potential therapeutic strategy to prevent the replication of coronavirus.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.0c00506