HIV-1 Protease As A Drug Target
With its integral role in HIV replication, HIV protease has been a prime target for drug therapy. HIV protease inhibitors work by specifically binding to the active site by mimicking the tetrahedral intermediate of its substrate and essentially becoming “stuck,” disabling the enzyme. This results in the production of immature proteins, which cannot assemble into infectious virions. Several protease inhibitors have been licensed for HIV therapy.
However, due to the high mutation rates of retroviruses, and considering that a few amino acid change within HIV protease can render it much less visible to an inhibitor, the active site of this enzyme can change rapidly when under the selective pressure of replication-inhibiting drugs.
One approach to minimizing the development of drug-resistance in HIV is to administer a combination of drugs composed of drugs which inhibit several key aspects of HIV’s replication cycle simultaneously, rather than one drug at a time. Other drug therapy targets include reverse transcriptase, virus attachment, membrane fusion, cDNA integration and virion assembly.
Read more about this topic: HIV-1 Protease
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