Few broad-spectrum antivirals exist. Here we describe an antiviral small molecule (LJ00I) effective against numerous enveloped viruses including filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, Influenza A, and HIV-1. In sharp contrast, the compound had no effect on the infection of non-enveloped viruses. These data suggest that LJ00I targets a component common to enveloped viruses. LJ00I specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited virus entry at a step after receptor binding. In vitro and in vivo assays demonstrated no overt toxicity. LJ001 also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure-activity relationship analyses implicate both the polar and non-polar ends of LJ00I in the antiviral activity. In sum, the data reveals a class of broad-spectrum antivirals that specifically targets and inactivates the viral lipid membrane. |