Molecular Playground/HIV Protease Inhibitor Enlarged

{{Template:MP_masthead}}

==AIDS Before Protease Inhibitors==

From 1981, when ''Acquired Immuno<b>d</b>eficiency Syndrome'' ([http://en.wikipedia.org/wiki/AIDS AIDS]) was first recognized<ref name="history">[http://www.avert.org/aids-history-86.htm History of AIDS up to 1986]</ref>, until the mid-1990's, the life expectancy of a person after infection with ''Human Immunodeficiency Virus'' ([http://en.wikipedia.org/wiki/HIV HIV]) was about 7-12 years<ref name="7years">[http://www.medicalnewstoday.com/articles/55870.php Lifetime Cost And Life Expectancy For Current HIV Care In The U.S.] (2006).</ref>, and even less for infants and children<ref>[http://www.baangerda.org/en/FAQ.html#h3 Care and treatment for HIV & AIDS orphans in Thailand: FAQ]</ref>. During this era, the available anti-HIV (anti-retroviral) drugs all worked on one target, the virus [[Reverse transcriptase|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==

In 1995, the US FDA approved the first [[HIV-1_protease|HIV protease]] inhibitor drug, [[HIV-1_protease|saquinivir]]<ref name="hivpis">[http://en.wikipedia.org/wiki/Hiv_protease_inhibitors HIV Protease Inihbitors at Wikipedia].</ref>, 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)<ref name="haart">[http://en.wikipedia.org/wiki/Haart HAART at Wikipedia].</ref>. HAART produced "an immediate and precipitous decline in HIV/AIDS mortality"<ref name="lifeexp">[http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9930 HIV Life Expectancy Approaching Normal] (2008).</ref>. 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<ref name="lifeexp" />.

==Ritonavir==

At right is shown the structure of Ritonavir&reg; <ref name="ritonavir">See also [http://en.wikipedia.org/wiki/Ritonavir Ritonavir at Wikipedia], and [http://ritonavir.com Ritonavir.Com].</ref> (<scene name='User:Eric_Martz/Molecular_Playground/HIVDrug/Hivpi_binding_simulationpdbgz/1'>restore initial scene</scene>),

an HIV protease inhibitor approved by the US FDA in 1996<ref name="hivpis" />. 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<ref name="saquinivir_wikipedia">[http://en.wikipedia.org/wiki/Saquinavir Saquinivir at Wikipedia].</ref>

==Molecular Playground Animation==

{{Template:Molecular Playground animation description}}

'''Methods.''' The ''Play Animation'' button above runs a [[Jmol]] command script, which was [[Molecular Playground/Authoring|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|atomic coordinate file]] ([[PDB file]]) displayed above ([[Image:Hivpi_binding_simulation.pdb.gz]]) contains 21 models, representing a simulation of the binding of Tamiflu to HIV protease. The simulation was done with [http://www.mdl.com MDL Sculpt] starting with [[1hxw]], which remains as the 21st model.

==See Also==

* [http://molviz.org MolviZ.Org] for visualization of other important 3D structures.

* [[Morphs]] for an introduction to visualization of macromolecular conformational changes.

==Notes==

<references />