Did you get your flu shot this year? Influenza is a leading cause of preventable death in the industrialized world, representing hundreds of billions of dollars in healthcare expenditures and loss of economic production. While the yearly influenza vaccination is nearly 90% effective at limiting infections in populations less than 65 years of age, there is insufficient evidence regarding the effectiveness of the flu shot for the elderly population, whose immune systems may not mount an adequate antibody response to vaccination. Beyond vaccination, front-line therapies such as the neuraminidase inhibitors Tamiflu and Relenza have proven to be of limited effectiveness due to the evolution of drug-resistant influenza mutants. Therefore, a need exists for the development of new therapies to circumvent these resistance mechanisms. Computational biologists employing NAMD and VMD used molecular simulations to uncover the key role that water plays in mediating how well antiviral drugs can bind to proteins of the influenza virus. This investigation, reported recently, reveals that amino-acid mutations responsible for drug resistance act by reshaping the local electric field and also by permitting infiltration of water within the otherwise hydrophobic drug binding pocket. These mutations thus induce drug resistance in much the same way as inverting the polarity of a magnet can repel rather than attract. These findings are expected to help guide the design of novel drugs with increased antiviral efficacy. Additional details about this study can be found here.