Ion channels are targeted by ~20% of currently licensed drugs, yet those encoded by viruses, “viroporins” are neglected by comparison. This is despite the clinical precedent of adamantane drugs targeting the influenza A virus (IAV) M2 proton channel. Viroporins play essential roles during the lifecycles of many pathogenic viruses yet, with few exceptions, precise understanding of their function within virion and/or host cell membranes remains limited. One major bottleneck has been limited usefulness of prototypic small molecule inhibitors.

Viroporins also perform non-channel related functions, confounding mutagenesis studies. Thus, we have focused upon improving small molecules as tools to investigate their properties. Druggable binding sites identified by prototypic drugs can be refined via an array of approaches yielding inhibitors with improved fidelity and utility. Iterative increases in both structural and functional understanding of viroporins can identify new biological roles, simultaneously forming a platform for future therapeutic discovery.