Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) especially in children. The majority of EV-A71 cases are mild, however, severe cases have exhibited an array of neurological complications which often lead to death. In a screening campaign to discover hits against EV-A71, we identified six 2,4-diaryl-substituted thiophene compounds that were previously reported as Dyrk1A inhibitors. From these, compound S43 (EC