INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY THE SULFONATED STILBENE DYE RESOBENE

The anti-HIV sulfonated dye, resobene, was found to be a potent inhibi tor of the attachment of HIV to target cells, the fusion of envelope- and CD4-expressing cells, and the cell-to-cell transmission of virus. Resobene inhibited the infection of phenotypically distinct, establish ed human cell lines and fresh human peripheral blood lymphocytes and m acrophages by laboratory-derived isolates of human immunodeficiency vi rus type 1 (HIV-1) and type 2 (HIV-2), and a panel of biologically div erse primary clinical isolates, including syncytium-inducing and non-s yncytium-inducing viruses and strains representative of the various vi rus clades found worldwide. The compound was also active against all d rug-resistant virus isolates tested. Cell-based and biochemical mechan ism of action studies demonstrated that the compound inhibits the atta chment of infectious virus and fusion of virus-infected cells to uninf ected target cells by binding to the cationic V3 loop of the envelope glycoprotein. Resobene effectively inhibited the infection of cell pop ulations which do and do not express cell surface CD4. Resobene preven ted infection of the cervical epithelial cell line ME180, suggesting t he compound may effectively act as a topical microbicide to prevent th e sexual transmission of HIV.