The Molecules of HIV

Note: this site last updated in 2006


An article from "The Molecules of HIV" (c) Dan Stowell

Integrase is HIV's enzyme for inserting the DNA version of its genome into the host cell's DNA. It catalyses the "cut-and-paste" operation of snipping the host DNA and attaching the proviral genome to the snipped ends.

There are three "domains" in this protein, in this order:

  • A "zinc finger" which is believed to help integrase form multimers (stable agglomerations of multiple integrase molecules)
  • The central catalytic domain
  • A domain which binds to DNA

Integrase carries out a function which is pretty much unique to retroviruses">retroviruses - human cells don't have any need to cut-and-paste bits of DNA into their genome. This means that the inhibition of integrase should be a good target for drug therapy, since it's not likely to interfere with the normal operation of human cells.

So why don't we use integrase inhibitors in HIV therapy? Current treatment usually involves reverse%20transcriptase%20inhibitors">reverse%20transcriptase">reverse transcriptase inhibitors and protease inhibitors.

The answer is simply that no integrase-inhibitor drug has yet made it through the various testing stages and been approved for clinical use. Some showed promise in test-tube experiments but didn't seem to work in a real living organism. Others show more promise, but have yet to pass through the clinical trial stages that are necessary before any drug can be approved for clinical use.

One type of integrase inhibitor which is currently being looked into is the diketo acids.

Written by
Dan Stowell

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