The structure of a complex of its core domain with a novel inhibitor has been determined, 12 which provide us a platform for the investigation and discovery of anti-AIDS agents.ĭicaffeoylquinic acids (DCQAs), isolated from traditional medicinal plants, 13, 14 are a novel class of integrase inhibitors. 11 HIV-1 integrase can be divided into three discrete domains, N-terminus, core, and C-terminus. 10 For instance, two integrase inhibitors, raltegravir and elvitegravir, have been shown to be promising in clinical trials, and the first has been recently made available for clinical practice. The HIV-1 integrase, responsible for the integration of the newly synthesized double-stranded viral DNA into the host genomic DNA, is a new and important target of potential clinical relevance. However, the ability of HIV to rapidly evolve drug resistance, together with toxicity problems, requires the discovery and development of new classes of anti-AIDS drugs.

Combination antiviral therapy with reverse transcriptase and protease inhibitors has shown the potential therapeutic efficacy of antiviral therapy for treatment of AIDS. It encodes three enzymes: reverse transcriptase, protease, and integrase. HIV-1 is the cause of the worldwide epidemic. 6 Two major types of HIV have been identified, HIV-1 and HIV-2. 4, 5Īcquired immunodeficiency syndrome is a set of symptoms and infections resulting from the damage to the human immune system caused by the human immunodeficiency virus (HIV).

2, 3 According to a report of the World Health Organization (WHO) and the Joint United Nations Programme on HIV and AIDS (UNAIDS), in 2007, an estimated 33.2 million people globally lived with the disease, and it killed an estimated 2.1 million people, including 330,000 children. 1 It is the fourth greatest killer and the most quickly spreading disease in recent history. Despite considerable investment and recent progress for treating this disease, anti-AIDS therapy still fails to be fully suppressive. Our study will be of help to design new pharmaceuticals for the treatment of AIDS.Īcquired immunodeficiency syndrome (AIDS) has been a serious, life-threatening health problem since it was first identified in 1981. Our computational modeling study demonstrated that the inhibitor of this compound on HIV integrase is likely to proceed by two different but equivalent mechanisms with one bound to the active site region of the enzyme and another docked into the binding pocket located on the other side of the catalytic site. 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 3,4-dicaffeoylquinic acid. They are therefore promising compounds for developing new anti-AIDS drugs. These compounds are potent inhibitors of HIV-1 replication in cultured cell lines and catalytic activities of integrase in vitro. Dicaffeoylquinic acids, isolated from traditional medicinal plants, are a novel class of integrase inhibitors.

Natural products have provided a source of new drug candidates for anti-AIDS therapy. Inhibitors of this enzyme have a great potential to complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. 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. 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.

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