CHAPTER 9: Virus‐coded Ion Channels as Antiviral Targets

Ion channels constitute effective drug targets for myriad human diseases. Thus, essential ion channels encoded by globally important viruses represent an important opportunity for intervention. However, efforts targeting ‘viroporins’ to date are limited, with a single clinical precedent of adamantanes targeting influenza M2 proton channels. M2 inhibitors both help and hinder perceptions of viroporins as drug targets, providing proof‐of‐principle on the one hand, but now being clinically inexpedient due to resistance. This is perhaps unsurprising as 20 years passed between their identification and defining their mode of action, making them the equivalent of early ‘hits’ by today’s standards. Historically, viroporin research has been hampered by combined inherent difficulties of membrane protein biology and virus culture, with a lack of structural information in many cases. Efforts to improve or identify new viroporin inhibitors have been similarly restricted, with most examples comprising a handful of prototypic molecules. However, growing research focus has allowed revisitation of viroporins as drug targets, developing screening technologies and rapidly expanding structural information. As such, viroporins retain significant potential as an untapped area in drug discovery, increasingly amenable to modern methods, and applicable to some of the most significant viral challenges to human health.