We have examined a novel betain-type fluoroalkylated oligomer, RD6-2198, for its inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) and respiratory syncytial virus (RSV) in cell cultures. We have found that the compound is a potent and selective inhibitor of these viruses. RD6-2198 inhibited the replication of HIV-1IIIB at a concentration of 0.85 microg/ml with a selectivity index greater than 59 in MT-4 cells. Furthermore, its 50% effective concentration (EC50) values for HSV-1, HSV-2 and RSV, were 0.51, 0.94 and 3.0 microg/ml, respectively. We found that the RD6-2198 suppressed the gp120-CD4 interaction (as monitored by an enzyme-linked immunosorbent assay (ELISA) method). RD6-2198 also inhibited the binding of anti-gp120 monoclonal antibody to gp120 expressed on MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1IIIB). However, the compound did not inhibit the interaction of anti-CD4 antibody with CD4. These results suggest that RD6-2198 interacts with the viral envelope glycoprotein and thereby inhibits the viral adsorption process. In addition, RD6-2198 was also found to suppress the proliferation of MOLT-4/IIIB cells. When applied topically, RD6-2198 at a concentration of 10 mg/ml completely protected mice from an intravaginal HSV-2 infection.