Inhibition of wild-type human immunodeficiency virus and reverse transcriptase inhibitor-resistant variants by Phyllanthus amarus

Substantial progress has been made in research on natural products which effectively inhibit HIV-1 replication. Many active compounds were isolated from traditionally used medicinal plants including Phyllanthus species. This study shows that aqueous as well as alcohol-based Phyllanthus amarus extracts potently inhibit HIV-1 replication in HeLa CD4(+) cells with 50% effective concentration (EC50) values ranging from 0.9 to 7.6 mug/ml. A gallotannin enriched fraction showed enhanced activity (0.4 mug/ml), and the purified gallotannins geraniin and corilagin were most active (0.24 mug/ml). HIV-1 replication was also blocked in CD4(+) lymphoid cells with comparable EC50 values. Applying a cell-based internalization assay, we could demonstrate 70-75% inhibition of virus uptake at concentrations of 2.5 mug/ml for the water/alcohol extract and geraniin. In addition, a concentration-dependent inhibition of HIV-1 reverse transcriptase (RT) could be demonstrated in vitro. The 50% inhibitory concentration (IC50) values varied from 1.8 to 14.6 mug/ml. The ability to inhibit replication of a variety of RT inhibitor-resistant HIV-1 strains points to the potential of P. amarus extracts, as natural products, in the chemotherapy of HIV infections. (C) 2002 Elsevier Science B.V. All rights reserved.