INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) REPLICATION BY DAPHNODORINS

Three flavans, daphnodorins A, B and C isolated from Dahpne odora THUNB. were tested for their abilities to inhibit human immunodeficiency virus type 1 (HIV-1(IIIB) replication in MT-4 cells. The effective concentrations (EC(50)) of daphnodorins A, B and C against HIV-1-induced cytolysis were 0.26+/-0.08, 1.8+/-0.6 and 3.6+/-0.5 mu g/ml, respectively. Also these three compounds showed inhibitory effects of p24 antigen in human peripheral blood lymphocytes; As compared with 2', 3'-dideoxycytidine 5'-triphosphate (DDC-TP), daphnodorin A and daphnodorin C had relatively weak inhibitory effects on the reverse transcriptase of HIV-1, while daphnodorin B did not show any inhibitory effect at concentrations up to 1000 mu g/ml. These three compounds showed marked inhibitory effects on syncytium formation between HIV-1(IIIB)-infected and uninfected MOLT-4 (clone 8) cells at 3-30 mu g/ml without inducing cytotoxicity. The concentrations of the compounds blocking syncytium formation were consistent with the effective concentrations (EC(50)) against HIV-induced cytolysis of MT-4 cells. These results, differing from reverse transcriptase inhibitors, suggest that the daphnodorins exert their anti-HIV-1 activity through inhibition of early events of viral replication including adsorption of the virions to the cells or the subsequent entry.