chicoric-acid and Acquired-Immunodeficiency-Syndrome

Despite the continuous advances made in antiretroviral combination therapy, AIDS has become the leading cause of death in Africa and the fourth worldwide. Today, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action. In this review, plant substances showing a promising anti-HIV activity are discussed according to the viral targets with which they interact. Most of these compounds, however, interfere with early steps in the HIV replication, such as the virus entry steps and the viral enzymes reverse transcriptase and integrase, whereas until now almost no plant compounds have been found to interact with the many other viral targets. Since some plant substances are known to modulate several cellular factors, such as NF-kappa B and TNF-alpha, which are also involved in the replication of HIV, their role as potential anti-HIV products is also discussed. In conclusion, several plant-derived antiviral agents are good candidates to be further studied for their potential in the systemic therapy and/or prophylaxis of HIV infections, most probably in combination with other anti-HIV drugs.

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; HIV Integrase Inhibitors; HIV Reverse Transcriptase; Molecular Structure; Plants, Medicinal; Virus Integration

Current pharmacological agents for human immunodeficiency virus (HIV) infection include drugs targeted against HIV reverse transcriptase and HIV protease. An understudied therapeutic target is HIV integrase, an essential enzyme that mediates integration of the HIV genome into the host chromosome. The dicaffeoylquinic acids (DCQAs) and the dicaffeoyltartaric acids (DCTAs) have potent activity against HIV integrase in vitro and prevent HIV replication in tissue culture. However, their specificity against HIV integrase in cell culture has been questioned. Thus, the ability of the DCQAs and DCTAs to inhibit binding of HIV type 1 (HIV-1) gp120 to CD4 and their activities against HIV-1 reverse transcriptase and HIV RNase H were studied. The DCQAs and DCTAs inhibited HIV-1 integrase at concentrations between 150 and 840 nM. They inhibited HIV replication at concentrations between 2 and 12 microM. Their activity against reverse transcriptase ranged from 7 microM to greater than 100 microM. Concentrations that inhibited gp120 binding to CD4 exceeded 80 microM. None of the compounds blocked HIV-1 RNase H by 50% at concentrations exceeding 80 microM. Furthermore, when the effects of the DCTAs on reverse transcription in acutely infected cells were measured, they were found to have no activity. Therefore, the DCQAs and DCTAs exhibit > 10- to > 100-fold specificity for HIV integrase, and their activity against integrase in biochemical assays is consistent with their observed anti-HIV activity in tissue culture. Thus, the DCQAs and DCTAs are a potentially important class of HIV inhibitors that act at a site distinct from that of current HIV therapeutic agents.

Topics: Acquired Immunodeficiency Syndrome; Caffeic Acids; Chlorogenic Acid; Cinnamates; HIV Envelope Protein gp120; HIV Integrase; HIV Integrase Inhibitors; HIV Reverse Transcriptase; HIV-1; Humans; Succinates; Tartrates