Human Immunodeficiency Virus type 1
Human immunodeficiency virus (HIV) infection has become a major health problem over the past few decades, despite the fact that it is a fairly non-contagious virus. One can live in close association with an HIV infected person without any fear of infection. Doing the same with a person who is suffers from influenza or tuberculosis is a rather bad idea. Until not too long ago however, being infected with HIV was akin to a death sentence because the target of the virus are the T cells of the immune system, our prime defense against infections. HIV has generated intense interest in the pharmaceutical industry and lead to the discovery of several efficient drugs. HIV is a retrovirus. Its genetic material is stored in a single strand of RNA. Once it has invaded the cell, a viral protein, reverse transcriptase, uses the host cell to generate DNA. Reverse transcriptase is therefore a good target for potential drugs. Initial HIV drug were derived from nucleotides and were efficient but exhibited serious side effects.
The structure here shows the transcriptase in complex with a nonnucleoside inhibitor, nevirapine. The structure of the protein itself is reminiscent of polymerases with a large and deep cleft for the RNA-DNA hybrid. The drug itself is tuck away inside the protein, deeply buried at the very end of this large cleft. In order to keep up with the ability of viruses to mutate in response to such inhibitors, a clear understanding of the interaction of an inhibitor with the protein and the ability to develop new inhibitors on the basis of such information is important. It is a cat-and-mouse game that the virus will win if we do not.
Protein Data Bank (PDB)
Author: Arno Paehler