Inhibitors of Viral Proteases

Cleavage of viral proteins by proteinases (proteases) is required at several stages in the viral replication cycle: activation of some viral enzymes, post-translational cleavage of the polyprotein product of polycistronic mRNA, activation of envelope fusion glycoproteins, and maturation of the virion. As many of the proteases are virus-coded, it should be possible to find or devise agents that specifically inhibit the viral protease without interfering with essentia] cellular proteases. The three-dimensional structure of the HIV aspartyl protease has been solved by X-ray crystallography, and several pharmaceutical companies are competing to produce different types of protease inhibitors, some of which are already undergoing clinical trials. One approach has been to synthesize peptides corresponding to the sequence on the gag-pol polyprotein that represents the cleavage site for the HIV protease; such peptides, or close analogs of the native sequence, bind to the active site of the enzyme and inhibit its activity. Unfortunately, they are often of low solubility, have low oral bioavailability, and are rapidly degraded in serum. Hence, following the precedent of the very effective class of oral antihypertensive drugs that inhibit the protease, angiotensin-converting enzyme, attempts are being made to produce a stable molecule that mimics the conformation of the peptide but without amide bonds

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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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