Today’s molecule is pretty crazy (not because of its structure which is mind numbingly complex) but because it has the potential to stop an epidemic.
Raltegravir, also known as Isentress, was discovered by Merck a few years ago and is an extremely powerful HIV drug. It was approved by the FDA in 2007 has been a huge hit ever since. In fact, it was the first integrase inhibitor on the market and has spurred research into that area in order to create a whole new class of integrase inhibitors.
Now HIV is a type of retrovirus, meaning that instead of carrying DNA, it instead contains RNA. Using some viral enzymes, the RNA from the virus is converted in cDNA which is then integrated into the host DNA. Following the insertion, the cell starts to make copies virus which then begin to bud off. HIV is so devastating because it targets the immune system, specifically the white blood cells. HIV doesn’t actually kill anyone, it just comprises the immune system to the point that it can’t fight off normally benign infections.
Raltegravir comes to the rescue by blocking the insertion of the viral cDNA into the host DNA. The virus typically carries an enzyme called integrase which it uses to insert the cDNA. This point is a critical fork in the road for the host cell. If it gets infected, there is no turning back as it now contains the viral genome. However, if integrase is somehow blocked, it would like if the cell never got infected in the first place.
Integrase contains a magnesium ion in its active site which it uses to help speed up the integration. Raltegravir works by binding to the magnesium ion which effectively prevents the enzyme from binding the host DNA and therefore preventing the viral cDNA from being taken up.
Now HIV mutates at an extremely fast rate which is why patients with HIV typically take a mix of antiretroviral drugs in order to combat all the potential mutations. The high mutation rate is also why its hard to find a “catch all” cure since what might work with one person could potentially not work with another.
Relevant to my forgotten dream of curing HIV. Must reblog.