Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus

  • Adv Sci (Weinh). 2023 Apr 24;e2206869. doi: 10.1002/advs.202206869.
Xinyu Miao  1  2 ,  Yinyan Yin  3  4  5 ,  Yulian Chen  1 ,  Wenhui Bi  1 ,  Yuncong Yin  1 ,  Sujuan Chen  1 ,  Daxin Peng  1  2  6  7 ,  Lizeng Gao  8 ,  Tao Qin  1  2  6  7 ,  Xiufan Liu  1  2
Affiliations
  • 1. College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
  • 2. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
  • 3. College of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
  • 4. International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
  • 5. Guangling College, Yangzhou University, Yangzhou, Jiangsu, 225000, P. R. China.
  • 6. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.
  • 7. Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease, Yangzhou, Jiangsu, 225009, P. R. China.
  • 8. CAS Engineering Laboratory for Nanozyme, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
PMID: 37092591 DOI: 10.1002/advs.202206869
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.

Keywords
ferroptosis; influenza virus; metastable iron sulfides; therapy.
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