Several strategies have been used to block flavivirus and alphavirus fusion reactions and thus inhibit virus infection. SFV and DENV fusion are specifically blocked by exogenous DIII, which binds to the core trimer and prevents the foldback of endogenous DIII and hairpin formation [41] . A later stage in DENV fusion is targeted by a stem-derived peptide, which binds to the ectodomain trimer in which DIII has folded back but stem packing has not yet occurred [58] . These virus protein-protein interactions can be reconstituted in vitro [29, 30, 58] , opening the possibility of using them as screens for small molecule inhibitors of virus fusion and infection.