Inhibitors of HIV-1 replication that inhibit HPV integrase

HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might he directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic acid, and L-chicoric acid, inhibit HIV-1 integrase in biochemical assays at concentrations ranging front 0.06-0.66 mu g/ml; furthermore, these compounds inhibit HIV-1 replication in tissue culture at 1-4 mu g/ml. The toxic concentrations of these compounds are fully 100-fold greater than their antiviral concentrations, These compounds represent a potentially important new class of antiviral agents that may contribute to our understanding of the molecular mechanisms anisms of viral integration, Thus, the dicaffeoylquinic acids are promising leads to new anti-HIV therapeutics and offer a significant advance in the search for new HIV enzyme targets as they are both specific for HIV-1 integrase and active against HIV-1 in tissue culture.