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双向调控不稳定铁硫化物对流感病毒的病毒和细胞铁死亡

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

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.

Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, 225009, P. R. China.

出版信息

Adv Sci (Weinh). 2023 Jun;10(17):e2206869. doi: 10.1002/advs.202206869. Epub 2023 Apr 24.

DOI:10.1002/advs.202206869
PMID:37092591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10265104/
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 Fe . 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.

摘要

流感病毒具有众多亚型和频繁变异，限制了高效广谱抗病毒策略的发展。在这里，开发了一种针对各种甲型/乙型流感亚型病毒的新型多抗病毒亚稳铁硫化物（mFeS）。本工作发现 mFeS 在保守的病毒包膜中诱导高水平的脂质过氧化和 •OH 自由基，这依赖于 Fe 。这种现象被称为病毒铁死亡，导致病毒在体外和体内的感染力和致病性丧失。此外，mFeS 的煎剂（Dc(mFeS)）通过纠正病毒诱导的重编程硫代谢来抑制细胞铁死亡依赖性的细胞内病毒复制，这是一种保守的细胞代谢。值得注意的是，负载 mFeS 的个人防护设备（PPE）可提供良好的抗病毒保护。mFeS 与煎剂联合雾化给药（mFeS&Dc）对小鼠 H1N1 致死性感染具有潜在的治疗效果。总之，mFeS 代表了一种具有广泛活性的抗病毒替代物，可针对细胞内和细胞外流感病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/a5bf59969db0/ADVS-10-2206869-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/d8d03f2893ff/ADVS-10-2206869-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/b0c0e0124151/ADVS-10-2206869-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/a5bf59969db0/ADVS-10-2206869-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/b751ee019720/ADVS-10-2206869-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/4d486f1c50dd/ADVS-10-2206869-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/fd7cdccfb027/ADVS-10-2206869-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc5/10265104/a5bf59969db0/ADVS-10-2206869-g003.jpg

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