Drugs for the Treatment of AIDS

Replication of the human immunodeficiency virus (HIV), the causative agent of AIDS, is susceptible to targeted interventions, because several virus-specific metabolic steps occur in infected cells (A). Viral RNA must first be transcribed into DNA, a step catalyzed by viral "reverse transcriptase." Double-stranded DNA is incorporated into the host genome with the help of viral integrase. Under control by viral DNA, viral replication can then be initiated, with synthesis of viral RNA and proteins (including enzymes such as reverse tran-scriptase and integrase, and structural proteins such as the matrix protein lining the inside of the viral envelope). These proteins are assembled not individually but in the form of polyproteins. These precursor proteins carry an N-ter-minal fatty acid (myristoyl) residue that promotes their attachment to the interior face of the plasmalemma. As the virus particle buds off the host cell, it carries with it the affected membrane area as its envelope. During this process, a protease contained within the polyprotein cleaves the latter into individual, functionally active proteins.

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