We have synthesized tri- and tetravalent sialic acid compounds and evaluated them in an Ad37 cell-binding assay.The most promising trivalent compound, ME0322, was subsequently shown to be a very potent inhibitor of Ad37 infection of human ocular cells.Our functional and structural data show that ME0322 efficiently blocks the adenovirus cell-binding protein, the fiber knob.Therefore, such compounds offer promise as antiviral drugs for the topical treatment of epidemic keratoconjunctivitis.