Sandbox 645: Difference between revisions
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*APPLICATIONS: | *APPLICATIONS: | ||
Currently there is no cure for HIV. However after some extensive research, some drugs were to be designed in order to pause the HIV affects. This happens by the ability of the drugs to mimic the tetrahedral intermediates in the active site and prevent the polypeptide from binding the Asp residues. | |||
, preventing the binding of polyproteins. Its chemical structure mimics the tetrahedral intermediate of the hydrolytic reaction, thereby <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'>interacting strongly with the catalytic Asp residues</scene>.<ref>PMID:17243183</ref> Saquinavir is essentially an uncleavable ligand, as indicated by the <scene name='User:David_Canner/Sandbox_HIV/Hiv_morph2/9'> similar conformational changes in the protease flaps </scene> on binding saquinavir or a polypeptide . Other drugs used to treat HIV infection that inhibit <scene name='User:David_Canner/Sandbox_HIV/Inhibitor_intro/1'>HIV protease</scene> include , , and . | |||
When a HIV virus infects an organism it tends to multiply within the body’s cells. The virus is then released to infect other cells. In this manner, the infection of HIV infects the newly made cells of the body. While the viruses are produced, proteins and enzymes used to manufacture the DNA in addition to other components of the virus are made. In this case, protease is that enzyme that is needed to bring the structural and enzymes of the virus together. Protease drugs are what could inhibit this virus. | When a HIV virus infects an organism it tends to multiply within the body’s cells. The virus is then released to infect other cells. In this manner, the infection of HIV infects the newly made cells of the body. While the viruses are produced, proteins and enzymes used to manufacture the DNA in addition to other components of the virus are made. In this case, protease is that enzyme that is needed to bring the structural and enzymes of the virus together. Protease drugs are what could inhibit this virus. | ||
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*HIV Drugs: | *HIV Drugs: | ||
1) Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site tunnel tightly, which will prevent polyproteins from also binding. | 1) Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_tunnel/1'> tunnel tightly </scene>, which will prevent polyproteins from also binding. Saquniavir's chemical structure has the ability to mimic the tetrahedral intermediate of the hydrolytic reaction to interact <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'> </scene>.[[Image:Saquin1.gif|frame|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]] Knowing that, Saquinavir is an uncleavable ligand by studying its similar conformational changes in binding saquinavir or a polypeptide. <ref>PMID: 20426757</ref> Two types of mutants can result as a way of depleting the effectiveness of the <scene name='User:David_Canner/Sandbox_HIV/Saquinavir/4'>Saquinavir</scene> ([[Invirase]]) drug. These mutants are G48V and G48V/L90M. They cause 13.5 and 149 fold reductions, respectively. Based on some quantum mechanical and molecular mechanical analysis of the interaction of the saquinavir interaction; a disturbance of the saquinavir with the mutant with a flap residue 48 leads to a change in the hydrogen bonding. This mutation leads to the loss in the inhibitor/ enzyme binding. | ||
2) Indinavir (Crixivan) this protease inhibitor is an oral medication that blocks the protease activity and leads to defect the viruses. Once these viruses are unable to reach the body’s cells, it will decrease in number[[Image:Indinav1.gif|frame|Ritonavir has a molecular weight of 711.88. It is very soluble in water and in methanol.]]This inhibitor doesn’t have the ability to prevent the HIV transmission among individuals, nor does it cure AIDS or HIV infection. | |||
<scene name='User:David_Canner/Sandbox_HIV/Indinavir/2'>Indinavir </scene> ([[Crixivan]])is approved by the FDA in March 1995. <ref>PMID: 11363398</ref> | |||
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3) Ritonavir (Norvir), has the same effect of indinavir on HIV protease. It was approved by the FDA in June 1999. This drug consists of capsules or tablets 100 mg; Solution: 80 mg/ml. It is recommended that adults consume 600 mg twice a day and then increase by 100 mg in every 2 days.[[Image:Ritonavirsol1.gif|frame|Ritonavir is soluble in isopropanol and practically insoluble in water.]] Ritonavir can interact with many drugs leading those drugs to increase or decrease in effectiveness. It increases the concentration of Mycobutin and Viagra; however, decrease the concentration of Demerol.<ref>PMID: 11708183 | 3) Ritonavir (Norvir) , has the same effect of indinavir on HIV protease. It was approved by the FDA in June 1999. This drug consists of capsules or tablets 100 mg; Solution: 80 mg/ml. It is recommended that adults consume 600 mg twice a day and then increase by 100 mg in every 2 days.[[Image:Ritonavirsol1.gif|frame|Ritonavir is soluble in isopropanol and practically insoluble in water.]] <scene name='User:David_Canner/Sandbox_HIV/Ritonavir/1'>Ritonavir</scene> ([[Norvir]]) can interact with many drugs leading those drugs to increase or decrease in effectiveness. It increases the concentration of Mycobutin and Viagra; however, decrease the concentration of Demerol.<ref>PMID: 11708183 | ||
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4) Nelfinavir (Viracept), Nelfinavir was approved by the FDA in March, 1997. Nelfinavir has not been effectively evaluated in pregnant women. Viracept prevents T-cells that have been infected with HIV from producing new HIV.[[Image:Nelfin1.gif|frame|Nelfinavir is slightly soluble in water at pH ≤ 4 and completely soluble in methanol.]] Usually given to patients through tablets. Each tablet contains inactive ingredients such as: calcium silicate, magnesium stearate, hypromellose, and triacetin.<ref>PMID: 11364528 | 4) Nelfinavir (Viracept), Nelfinavir was approved by the FDA in March, 1997. <scene name='User:David_Canner/Sandbox_HIV/Nelfinavir/2'>Nelfinavir</scene> ([[Viracept]]) has not been effectively evaluated in pregnant women. Viracept prevents T-cells that have been infected with HIV from producing new HIV.[[Image:Nelfin1.gif|frame|Nelfinavir is slightly soluble in water at pH ≤ 4 and completely soluble in methanol.]] Usually given to patients through tablets. Each tablet contains inactive ingredients such as: calcium silicate, magnesium stearate, hypromellose, and triacetin.<ref>PMID: 11364528 | ||
</ref> | </ref> | ||