Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents

Newly developed antiviral compounds consisting of an adamantane derivative chemically linked to a water-soluble polyanionic matrix were shown to inhib it HIV-1 infection in lymphoblastoid cells, HeLa CD4 + beta-galactosidase ( MAGI) cells and macrophages. The effect of the compounds was recorded by me asuring viral reverse transcriptase activity and p24 by ELISA in culture su pernatant and by immunoblotting of cell lysates. In this paper we describe the data obtained with one of the most promising compounds, Amant. Amant wa s not toxic for the host cells at concentrations as high as 1 mg/ml. The in hibition of HIV-1 replication in MT-4 and MAGI cells was observed when Aman t was added either before infection or with the virus (0 h of infection), a nd was expressed even when the compound added at 0 h was removed 1.5 h afte r infection. Its inhibitory concentration (IC50) against HIV-1 and HIV-2 re plication was 2-6 and 93 mu g/ml, respectively. The anti-HIV-1 effect of th e compound was gradually decreased when it was added 1 and 2 h post infecti on, and no inhibition was observed when the compound was added 4 h after in fection, suggesting that the compound as a membranotropic drug blocks an ea rly step of replication. It completely prevented the transport of Gag prote ins into the nuclei. Pretreatment of the virus with Amant did not reduce it s infectious activity. The classical adamantane derivatives amantadine and rimantadine hydrochloride did not inhibit HIV replication. (C) 1999 Elsevie r Science B.V. All rights reserved.