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Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus
Xinyu Miao1,2, Yinyan Yin3,4,5, Yulian Chen1
1College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
Abstract:
Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.
Insights
A novel iron sulfide (mFeS) material induces viral ferroptosis, effectively neutralizing influenza viruses. This broad-spectrum antiviral agent shows promise for personal protective equipment and therapeutic applications against influenza infections.
Area of Science:
- Materials Science
- Virology
- Nanotechnology
Background:
- Influenza viruses exhibit frequent variation, complicating the development of effective antiviral strategies.
- Existing antiviral approaches face challenges due to the diverse subtypes and rapid evolution of influenza viruses.
Purpose of the Study:
- To develop a novel, broad-spectrum antiviral agent against influenza A and B viruses.
- To investigate the mechanism of action of metastable iron sulfides (mFeS) against influenza viruses.
Main Methods:
- Synthesis and characterization of metastable iron sulfides (mFeS).
- In vitro and in vivo evaluation of mFeS antiviral activity against influenza viruses.
- Investigation of mFeS-induced viral ferroptosis and its effect on viral infectivity and pathogenicity.
- Assessment of mFeS decoction (Dc(mFeS)) on intracellular viral replication and cellular sulfur metabolism.
- Evaluation of mFeS-loaded personal protective equipment (PPE) and aerosol administration of mFeS & Dc(mFeS) in a mouse model.
Main Results:
- mFeS induces viral ferroptosis via Fe2+-dependent lipid peroxidation and •OH radical generation in the viral envelope, leading to loss of infectivity.
- Dc(mFeS) inhibits intracellular viral replication by correcting virus-induced alterations in cellular sulfur metabolism.
- mFeS-loaded PPE demonstrated effective antiviral protection.
- Aerosol administration of mFeS & Dc(mFeS) showed therapeutic potential against H1N1 influenza infection in mice.
Conclusions:
- mFeS is a novel antiviral agent with broad-spectrum activity against intracellular and extracellular influenza viruses.
- Viral ferroptosis induced by mFeS offers a new mechanism for influenza virus inactivation.
- mFeS and its formulations hold potential for both preventative (PPE) and therapeutic applications against influenza.
