Molecular Playground/HIV Protease Inhibitor

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The movie on this page is out of order. Once it has been fixed, this notice will be removed. Eric Martz 23:48, 7 November 2020 (UTC)

About this image
Molecular Playground at the University of Massachusetts. MOVIE.


AIDS Before Protease Inhibitors

From 1981, when Acquired Immunodeficiency Syndrome (AIDS) was first recognized[1], until the mid-1990's, the life expectancy of a person after infection with Human Immunodeficiency Virus (HIV) was about 7-12 years[2], and even less for infants and children[3]. During this era, the available anti-HIV (anti-retroviral) drugs all worked on one target, the virus reverse transcriptase. The limited scope of these drugs made it easier for HIV to develop resistance to the drugs available at the time.

HIV Protease Inhibitors: A Breakthrough

HIV Protease and Inhibitor Drug Ritonavir

Drag the structure with the mouse to rotate

In 1995, the US FDA approved the first HIV protease inhibitor drug, saquinivir[4], which was the first anti-retroviral drug with a completely different target. Hence it was deemed to be in a new second class of antiretroviral drugs. Combining an HIV protease inhibitor with two or more reverse transcriptase inhibitors was called highly active anti-retroviral therapy (HAART)[5]. HAART produced "an immediate and precipitous decline in HIV/AIDS mortality"[6]. Although young people infected with HIV may still have their lives shortened by 15-25 years, the life expectancy of HIV-positive people for whom optimal drug therapy is available is now 24 years or more[6].


At right is shown the structure of Ritonavir® [7] (), an HIV protease inhibitor approved by the US FDA in 1996[4]. Ritonavir, the second HIV protease inhibitor to be approved by the FDA, improved the efficacy of the first, saquinivir, when the two were given together, by slowing the inactivation of saquinivir[8]

Molecular Playground Animation


You may rotate the molecule at any time during the animation.
There is also a LARGER version of this animation.

The Molecular Playground interactive projection in the Integrated Sciences Building at the University of Massachusetts, Amherst, USA, shows the molecular display that you see when you press the button above. This is only one of a series of modules that are shown. Instructions for authoring modules that display molecules in Molecular Playground are available.

Methods. The Play Animation button above runs a Jmol command script, which was authored by hand, and uploaded to Proteopedia. You can examine the script at Image:MP hivdrug.spt, which uses Image:MPSupportVersion01.spt (see Molecular Playground/Authoring). The atomic coordinate file (PDB file) displayed above (Image:Hivpi binding simulation.pdb.gz) contains 21 models, representing a simulation of the binding of Ritonavir to HIV protease. The simulation was done with MDL Sculpt starting with 1hxw, which remains as the 21st model.

See Also

Additional Resources

For additional information, see: Human Immunodeficiency Virus


  1. History of AIDS up to 1986
  2. Lifetime Cost And Life Expectancy For Current HIV Care In The U.S. (2006).
  3. Care and treatment for HIV & AIDS orphans in Thailand: FAQ
  4. 4.0 4.1 HIV Protease Inihbitors at Wikipedia.
  5. HAART at Wikipedia.
  6. 6.0 6.1 HIV Life Expectancy Approaching Normal (2008).
  7. See also Ritonavir at Wikipedia, and Ritonavir.Com.
  8. Saquinivir at Wikipedia.

Proteopedia Page Contributors and Editors (what is this?)

Eric Martz, David Canner

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