Palmitic Acid Is a Novel CD4 Fusion Inhibitor That Blocks HIV Entry and Infection

Abstract The high rate of HIV-1 mutation and the frequent sexual transmission highlight the need for novel therapeutic modalities with broad activity against both CXCR4 (X4) and CCR5 (R5)-tropic viruses. We investigated a large number of natural products, and from Sargassum fusiforme we isolated and identified palmitic acid (PA) as a natural small bioactive molecule with activity against HIV-1 infection. Treatment with 100 μM PA inhibited both X4 and R5 independent infection in the T cell line up to 70%. Treatment with 22 μM PA inhibited X4 infection in primary peripheral blood lymphocytes (PBL) up to 95% and 100 μM PA inhibited R5 infection in primary macrophages by over 90%. Inhibition of infection was concentration dependent, and cell viability for all treatments tested remained above 80%, similar to treatment with 10−6 M nucleoside analogue 2′, 3′-dideoxycytidine (ddC). Micromolar PA concentrations also inhibited cell-to-cell fusion and specific virus-to-cell fusion up to 62%. PA treatment did not res...