Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine

Abstract The IBOGA alkaloid congener 18-methoxycoronaridine (18-MC) exhibits IN VITRO leishmanicidal and IN VIVO anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations. The antiretroviral activity of 18-MC resulted in EC 50 values of 22.5 ± 4.7 μM and 23 ± 4.5 μM for R5 and X4 isolates, respectively, in PBMCs, and a therapeutic index (TI) of 14.5. Similar findings were observed for inhibition of HIV-1 replication in macrophages: EC 50 equal to 12.8 ± 5 μM and 9.5 ± 3 μM for an R5 virus after 14 and 21 days of infection, respectively, with TI equal to 25.6 and 34.5. 18-MC moderately inhibits the HIV-1 enzyme reverse transcriptase (IC 50 = 69.4 μM), which at least partially explains its antiretroviral activity.