Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives

Abstract

Ion channels play key roles in almost all facets of cellular physiology and have emerged as key host cell factors for a multitude of viral infections. A catalogue of ion channel-blocking drugs have been shown to possess antiviral activity, some of which are in widespread human usage for ion channel-related diseases, highlighting new potential for drug repurposing. The emergence of ion channel–virus interactions has also revealed the intriguing possibility that channelopathies may explain some commonly observed virus induced pathologies. This field is rapidly evolving and an up-to-date summary of new discoveries can inform future perspectives. We herein discuss the role of ion channels during viral lifecycles, describe the recently identified ion channel drugs that can inhibit viral infections, and highlight the potential contribution of ion channels to virus-mediated disease.

Mini-review: antibody therapeutics targeting G protein-coupled receptors and ion channels

“…Here, the main opportunities can be found in the oncology, pain (including migraine) and autoimmune/inflammation therapeutic areas, although other significant targeting opportunities are presented by metabolic, respiratory disease genetic/rare or neglected disease indications and a modest number in fibrosis, ophthalmology and infectious disease. The role of ion channels in infectious diseases is also being explored further and an area of emerging biology [ 13 ]. In fact, many viruses encode their own ion channels, which emphasize the importance of ionic balance during viral infection [ 14 ].…”

“…Ironically, based on current literature and recent epidemiological evidence, smoking status appears to provide a protective role against COVID-19 infection, suggesting that the nicotinic acetylcholine receptor could also present a potential therapeutic target [ 16 ]. Several other ion channels have also been identified as potential targets for infectious disease indications in a recent review [ 13 ], including the calcium two-pore channel 2 for SARS-CoV-2 [ 17 ].…”

Deciphering the interactions of SARS-CoV-2 proteins with human ion channels using machine learning-based method

“…The dearth of approved treatment therapeutic strategies specific for SARS-CoV-2 infection impeded disease containment measures and control of the spread of infection. Viruses with small-sized genomes in particular, depend on the host genomic machinery for many of their essential functions via interacting with membrane proteins and regulating HICs (3). HICs are transmembrane proteins which allow the passive flow of ions in and out of cells and cellular organelles owing to their electrochemical gradient.…”

“…Dysfunction of HICs leads to a class of diseases called channelopathies (4). Numerous viral infections are involved in neuronal pathologies, diarrhoea, cardiomyopathies, bronchitis and pain disorders exploiting a variety of HICs (3).…”

“…Thus, HICs interacting with viral proteins are likely to be more effective antiviral targets. Moreover, the development of HIC-viral interactions has provided an insight that channelopathies may explain some commonly observed virus induced pathologies (3). At present 13% of the clinically approved drugs are ion channel modulators, presenting the hypothesis that ion channels targets could give promising pharmacological results for the alteration of the viral life cycle (7).…”