Here we report that GA shows antiviral activity against Herpes simplex virus 1 (HSV-1), Human cytomegalovirus (HCMV), and Zika virus (ZIKV) primarily through viral fusion inhibition. In addition, we show inhibition of entry of a replication-defective non-enveloped adenovirus. The antiviral effects were observed below the cytotoxic threshold. We believe that broad spectrum antiviral activity is achieved through the inhibition of viral entry and that this effect could be therapeutically utilized systemically in the context of severe acute viral disease, or topically for the treatment of cutaneous viral lesions. We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins13 including: pathogenic human enveloped viruses from Class I (ZIKV, HIV, EBOV, and influenza A virus (IAV)), Class II (Venezuelan equine encephalitis virus (VEEV) and Semliki Forest virus (SFV)), and Class III (vesicular stomatitis virus (VSV) and Epstein Barr virus (EBV)). Taken together, our experiments suggest that GA inhibits viral entry by blocking the initial fusion event.