Computational investigation of the anti-HIV activity of Chinese medicinal formula Three-Huang Powder.

An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is integration of the double-stranded retroviral DNA into the genome of the host cell. HIV-1 integrase, the enzyme that inserts the vital DNA into the host chromosome, is an attractive and rational target for anti-AIDS drug design because it is essential for HIV replication and there are no known counterparts in the host cell. Inhibitors of this enzyme have the great potential to complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. Natural products have provided a source of new drug candidates for anti-AIDS therapy. Baicalein and baicalin, identified components of a Chinese herbal medicine Scutellaria baicalensis Georgi, have been shown to inhibit infectivity and replication of HIV. They are therefore promising lead compounds for developing new anti-AIDS drugs. To understand how the inhibitors work and therefore design more potent and specific inhibitors, we have used molecular modeling techniques to investigate the binding modes of these inhibitors. The three-dimensional structures of these inhibitors were first built. Then, computational binding studies of these inhibitors, based on the crystal structure of the HIV-1 integrase catalytic domain, were performed to study the complex structure. The preliminary results of our computational modeling study demonstrated that Baicalein binds to the active site region of the HIV-1 integrase. Our study will be of help to identify the pharmacophores of inhibitors binding to HIV-1 integrase and design new pharmaceuticals for the treatment of AIDS.