Enterovirus D68 (EV-D68) is a poorly characterized member of the Enterovirus genus that is responsible for recent outbreaks of respiratory illness worldwide, yet no antiviral treatment is available. Liu et al. solved the crystal structure of EV-D68 and showed that the capsid canyon — a deep surface depression that is the site of host receptor binding — is shallower and narrower than that of other enteroviruses. Similarly to other enteroviruses, the EV-D68 canyon is occupied by a pocket factor, a fatty acid that stabilizes the virus by preventing viral uncoating during transmission. The authors showed that pleconaril — an antiviral compound originally designed to inhibit rhinoviruses by binding to and stabilizing the capsid canyon — replaces the pocket factor of EV-D68 and fills the capsid canyon, probably blocking receptor binding and preventing viral uncoating. These data establish pleconaril as a possible drug candidate to treat EV-D68 infections.