HIV, or human immunodeficiency virus, is transmitted mostly from sexual activity and blood, such as from unclean needles. It damages the immune system by attacking immune cells. The virus enters cells, divides, destroys the cells, re-enters the blood and infects more cells. In order to divide and complete its life-cycle, HIV uses special proteins called enzymes. Enzymes are like little machines that carry out chemical reactions. Protease is one such enzyme. Protease helps HIV replicate; medications have been developed to inhibit this enzyme. It is important to consult a physician for the management of infections and other health conditions.
Function
Protease is necessary for the life cycle of HIV. The cells of the body, including the immune cells infected by HIV, normally create a copy of a section of DNA from RNA, and then use the RNA copy to make protein. HIV hijacks the cell's machinery to create its own proteins. When HIV proteins are made, they are all linked together and need to be separated to function. The enzyme that separates the linked proteins is HIV protease.
Mechanism
HIV protease is made up of amino acids, like any other protein. Part of the enzyme has electrically charged areas in a section of the enzyme called the active site. This site magnetically binds to the linked HIV proteins and breaks the chemical bonds between the proteins, effectively pulling them apart.
Inhibitors
Drugs called HIV protease inhibitors, include atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir and others. These drugs bind to the active site on HIV protease by mimicking the site on the linked HIV proteins that is normally bound to HIV protease. Once bound by the drug, HIV protease can no longer bind to the HIV proteins to unlink them.
Mutation
Unfortunately, HIV is able to mutate frequently, changing the structure of HIV protease. This can prevent the protease inhibitors from binding to HIV protease. The virus is able to adapt and become drug resistant, diminishing the effectiveness of the drugs.
Effectiveness and Side Effects
Mutation of HIV renders single drug therapy quite ineffective. Multiple drugs, usually three classes and sometimes more, are given to increase the effectiveness of treatment. Side effects may include gastrointestinal problems, fat and cholesterol abnormalities, development of diabetes and abnormal heart conduction.
References
- "Lehninger Principles of Biochemistry"; David L. Nelson, et al.; 4th Ed 2004
- "Harrison's Principles of Internal Medicine"; Anthony S Fauci, et al.; 17th Ed 2008
- "Basic and Clinical Pharmacology"; Bertram Katzung, et al.; 11th Ed 2009
