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Can iron chelators ameliorate viral infections?

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Abstract

The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.

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Acknowledgements

The authors wish to thank the financial support from the CNPq, under Contract Number 150539/2022-3 and from FAPESP, under Contracts Number 2018/19684-0 and 2021/10894-5.

Funding

This research was funded by the National Council for Scientific and Technological Development (CNPq) under contract number 150539/2022-3 and by The São Paulo Research Foundation (FAPESP), in Brazil, contracts number 2018/19684-0 and 2021/10894-5.

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Conceptualization, TAP and BPE; methodology, TAP and BPE; resources, TAP and BPE; data curation, BPE; writing—original draft preparation, TAP; writing—review and editing, TAP and BPE; supervision, BPE; project administration, TAP; funding acquisition, TAP and BPE All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tatiana Araujo Pereira.

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Pereira, T.A., Espósito, B.P. Can iron chelators ameliorate viral infections?. Biometals 37, 289–304 (2024). https://doi.org/10.1007/s10534-023-00558-x

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