ROS-mitochondria-NLRP3/STING axis mediates the enhanced anti-coronavirus activity of ZIF8 nanoparticles

Area of Science:

• Nanotechnology for antiviral therapeutics
• Materials science in virology
• Innate immune system modulation

Background:

• Coronaviruses (CoVs) present significant global health risks.
• Existing antiviral strategies often lack broad-spectrum efficacy or rapid deployment.
• Need for immune-independent antiviral interventions.

Purpose of the Study:

• To develop and evaluate zeolitic imidazolate framework-8 (ZIF8) as a novel zinc-based nanoagent for combating coronaviruses.
• To elucidate the underlying antiviral mechanisms of ZIF8.
• To assess the broad-spectrum efficacy and in vivo protective potential of ZIF8 against various CoVs.

Main Methods:

• Synthesis and characterization of ZIF8 nanoparticles.
• In vitro antiviral assays using porcine epidemic diarrhea virus (PEDV) and other CoVs (BCoV, IBV, PDCoV).
• Mechanistic studies involving reactive oxygen species (ROS) levels, mitochondrial function, NLRP3 inflammasome, and STING signaling.
• In vivo efficacy evaluation in a porcine deltacoronavirus (PDCoV)-infected mouse model.

Main Results:

• ZIF8 demonstrated superior antiviral activity compared to zinc oxide (ZnO).
• ZIF8 modulated ROS accumulation, preserved mitochondrial homeostasis, and promoted cytosolic mtDNA release.
• ZIF8 activated NLRP3 inflammasome and STING signaling pathways, enhancing host antiviral responses.
• ZIF8 exhibited broad-spectrum inhibition against α-, β-, γ-, and δ-coronaviruses.
• In vivo studies showed ZIF8 effectively reduced viral load and intestinal damage in a PDCoV mouse model under both preventive and therapeutic conditions.

Conclusions:

• ZIF8 is a promising broad-spectrum antiviral nanoagent against coronaviruses.
• The ROS-mitochondria-NLRP3/STING axis is crucial for ZIF8's antiviral mechanism.
• ZIF8 offers a novel platform for developing next-generation nanomaterial-based antiviral therapeutics.