The influenza A virus infects host cells using a membrane-embedded channel, M2. Its core is an histidine/water cluster that selectively conducts protons. Amphiphilic drugs such as amantadine prevent access to external water: however, pervasive drug-resistant mutations rendered them ineffective against nearly all flu strains. Using a molecular dynamics-based approach, we developed the first inhibitor against one of the resistant strains (JACS 133:12834, 2011), and present a widely portable strategy to model water molecules when designing against seemingly 'undruggable' targets.

Molecular dynamics simulation directed rational design of inhibitors targeting drug-resistant mutants of influenza A virus M2

244th National Meeting (2012)

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