Retro-2 is a selective inhibitor of retrograde protein trafficking mediated by syntaxin-5 at the interface between the endosome and trans-Golgi network, with no discernable effects on other intracellular trafficking pathways. Retro-2 inhibits ebolavirus infection with an EC50 value of 12.2 μM and reduces ricin-induced toxicity by 2.7-fold when used at a concentration of 20 μM in HeLa cells. Retro-2 also blocks JC polyomavirus, BK polyomavirus, and SV40 infectivity in Vero green monkey kidney epithelial cells in vitro (EC50s = 28.4, 61.2, and 58.6 μM, respectively). In mouse models, Retro-2 improves survival and reduces symptoms following infection with Shiga toxin-producing E. coli when administered at a dose of 100 mg/kg and protects against ricin challenge when administered prophylactically at a dose of 2 mg/kg.
