Zanamivir

<applet load="" size="450" color="" frame="true" spin="on" Scene ="Amprenavir/Amprenavi/2" align="right" caption="Amprenavir, better known as Agenerase, ([[3nu4]])"/>

===Better Known as: Agenerase===

* Marketed By: GlaxoSmithKline<br />

* Major Indication: [[Human Immunodeficiency Virus]] Infection<br />

* Drug Class: [[HIV Protease]] Inhibitor

* Date of FDA Approval (Discontinued): 1999 (2004) <br />

* 2004 Sales: ~$50 Million

* Importance: It was the first [[HIV Protease]] inhibitor which required only twice-a-day dosing as opposed to every 8 hours. It was replaced by a longer acting prodrug version called [[Fosamprenavir]].

When [[HIV]] first infects someone, it directs the synthesis of several polyproteins. The maturation of the virus to its infectious form requires that these polyproteins be cleaved to their component proteins by [[HIV Protease]]. The subunits of <scene name='Amprenavir/Protease/1'>HIV Protease</scene> come together to form a catalytic tunnel capable of tightly binding the nascent peptides and cleaving them into their mature, infectious form. Within this tunnel lies <scene name='Amprenavir/Proteasec/1'>two Asp-Thr-Gly conserved sequences</scene>, which contain the <scene name='Amprenavir/Proteasecas/2'>catalytic Asp residues</scene>. These catalytic Asp residues carry out the hydrolytic cleavage of the polyprotein. Amprenavir <scene name='Amprenavir/Bound/1'>binds specifically</scene> to these conserved sequences within the HIV Protease tunnel, preventing the nascent polyproteins from entering. Unable to actively cleave the nascent proteins into their infectious form, HIV is unable to mature and proliferate, allowing the patients immune system to fight off the infection more easily.<ref>PMID:1799632</ref><ref>doi:10.1038/nrd1907</ref>

===Drug Resistance===

The biggest difficulty with treating [[HIV]] is the rapidity at which it mutates and becomes resistant to treatments. To view a comprehensive and interactive analysis of the mutations which confer drug resistance to [[HIV Protease]], See: [[HIV Protease Inhibitor Resistance Profile]]