GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration

Glycosphingolipids (GSLs) are involved in HIV-1 entry. GM-3 ganglioside, a widespread GSL, affects HIV entry and infection in differentways, depending on the concentration, through its anchoring activity in lipidrafts. This explains why the induction of an altered GSLs metabolism was atempting approach to reducing HIV-1 cell infection. This study assayed thebiological properties of a synthetic GM-3 lactone mimetic,1, aimed atblocking HIV-1 infection without inducing the adverse events expected by analtered metabolism of GLSs in vivo. The mimetic, conjugated toimmunogenic protein ovalbumin and multivalently presented, was able tobind the CD4 molecule with high affinity and block its engagement withgp120, thus inhibiting virus entry. Elicited antimimetic antibodies were alsoable to block HIV-1 infection in vitro, with activity complementary to thatobserved for1. These preliminary results show that the use of GSLs mimeticscan be a novel promising mode to block HIV-1 infection and that1and otherGSL mimetics deserve further attention.