A small molecule that targets influenza Many of us rely on seasonal vaccines for protection against influenza and are only too aware of their limited breadth. Broadly neutralizing antibodies (bnAbs) that target the conserved hemagglutinin (HA) stem of the influenza virus provide hope for the development of universal vaccines and are being evaluated in clinical trials. Van Dongen et al. selected and optimized a small-molecule lead compound that recapitulates key interactions of the bnAb with HA. Like the bnAb, the compound inhibited viral fusion in the endosomes of target cells. The compound protected mice from influenza after oral administration and neutralized virus infection in a 3D cell culture of human bronchial epithelial cells. Science , this issue p. eaar6221