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HIV Inhibitors- A Temporary Cure
HIV- Human Immunodeficiency Virus is a type of virus that destroys the body’s immune system, which in turn makes it harder to fight off infectious diseases. A class of HIV protease inhibitors that are used to fight the HIV enzyme have become useless because resistance against them have been acquired by the enzyme. An inhibitor is a compound that binds to an enzyme and stops its activity, hence products are not formed. The HIV enzyme is used in the last stage of viral replication and binds to the protein substrate and cuts it up, then making more pieces to build more virus. The Proteins produced by the genetic material of HIV is much larger than the protein need to make viruses and must be cleavage.
The way the HIV protease inhibitor works is that, it is a transition state analogue. It is a chemical compound with a chemical structure that resembles the transition state of the substrate that the HIV enzyme binds to. The chemical reaction would not occur so the inhibitor ends up binding to the active site. Because the enzyme lowers the activation energy, when the transition state analogue aka inhibitor binds to its active site binds much stronger to the enzyme than a normal substrate because it doesn’t undergo a catalyzed reaction.
HIV is a very complex disease that it hard to resist. Because of its fast rate of mutation, scientists thought that they could use this to their advantage. They thought that sooner rather than later the virus would mutate in order to resist the inhibitor and hence the substrate to which it binds would also be resisted, they were wrong.
They were wrong because when Celia Schiffer of the university of Massachusetts Medical School crystallized the substrate and compared it to the enzymes structure she realized that the inhibitor contained protruding sides which were more important to the drug to carry out binding than to binding to the active site. Hence if the enzyme were to mutate its job would be unaffected by the drug. Schiffer explains that when the drug was being made its inhibiting properties were studies in more detail than how it actually binds. This was therefore a part time solution to a long-term virus. Inhibition can only work for so long until the virus mutates again.