It’s likely to take a molecule that’s more polar than researchers expected to stop human enterovirus 71, an RNA virus that can cause fatal brain inflammation and polio-like paralysis in children. The virus most commonly leads only to mild illness, including mouth sores, fever, and skin rash, but large outbreaks have been reported throughout the Asia-Pacific region and are being tracked by public health agencies including the Centers for Disease Control & Prevention. To learn more about how to combat the virus, Pavel Plevka and Michael G. Rossmann of Purdue University and colleagues teamed with Jane Cardosa of Malaysia’s Sentinext Therapeutics to determine the virus’s X-ray crystal structure (Science, DOI: 10.1126/science.1218713 ). Their structure had multiple similarities to those of related enteroviruses, including poliovirus. However, a key pocket involved in enterovirus 71 infection is shallower than its relatives’, and its associated small-molecule “pocket factor” is partially exposed to solvent as a result. The team suggests that antivirals designed to bind in this pocket may have to incorporate a hydrophilic head group, unlike other enterovirus inhibitors, which are completely hydrophobic because they end up buried in the other viruses’ deeper pockets.