Royal College of Surgeons in Ireland
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Unravelling the immunomodulatory effects of viral ion channels, towards the treatment of disease

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Version 2 2022-07-22, 10:34
Version 1 2022-03-11, 17:27
journal contribution
posted on 2022-07-22, 10:34 authored by Siobhan Gargan, Nigel Stevenson
The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed "Viroporins". They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains. Consequently, they can facilitate the transport of ions through the hydrophilic core. Viroporins localise to host membranes such as the endoplasmic reticulum and regulate ion homeostasis creating a favourable environment for viral infection. Viroporins also contribute to viral immune evasion via several mechanisms. Given that viroporins are often essential for virion assembly and egress, and as their structural features tend to be evolutionarily conserved, they are attractive targets for anti-viral therapeutics. This review discusses the current knowledge of several viroporins, namely Influenza A virus (IAV) M2, Human Immunodeficiency Virus (HIV)-1 Viral protein U (Vpu), Hepatitis C Virus (HCV) p7, Human Papillomavirus (HPV)-16 E5, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Open Reading Frame (ORF)3a and Polyomavirus agnoprotein. We highlight the intricate but broad immunomodulatory effects of these viroporins and discuss the current antiviral therapies that target them; continually highlighting the need for future investigations to focus on novel therapeutics in the treatment of existing and future emergent viruses.


Science Foundation Ireland, grant number SFI 19/FFP/6483



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Published Citation

Gargan S, Stevenson NJ. Unravelling the immunomodulatory effects of viral ion channels, towards the treatment of disease. Viruses 2021;13(11):2165.

Publication Date

27 October 2021

PubMed ID



  • RCSI Bahrain




  • Published Version (Version of Record)