- Assembly of new virus particles from nucleic acids and proteins (from steps 4 and 5)
(blocked by rifampin (9.4)) - Release and extrusion of the virus from the host cell
(blocked by neuraminidase inhibitors)
Although any of these seven steps could be a druggable target, most of the antiviral
agents clinically employed for non-AIDS infections act on the synthesis or assembly of
either purines or pyrimidines (steps 3 and 4). For AIDS, reverse transcriptase inhibitors
block transcription of the HIV RNA genome into DNA, thereby preventing synthesis
of viral mRNA and protein; protease inhibitors act on the synthesis of late proteins
(steps 5 and 6).
9.3.1 Antivirals Targeting Purine or Pyrimidine BiosynthesisIn the host cell, viruses induce the formation of enzymes that they themselves cannot
produce. The most important group of such enzymes is that of the DNA polymerases,
but thymidine kinase is also essential. Interference with these enzymes by either
enzyme inhibitors or through fraudulent antimetabolitesis the basis of the activity of
many antiviral drugs. In this respect, antiviral compounds and cytostatics used in the
treatment of malignant tumors have much in common and indeed overlap each other in
their activity.
Viral DNA polymerase is an important catalyst for the synthesis of viral nucleic
acids. DNA polymerase inhibitors have already been encountered as antitumor agents.
Ara-A (9.5, vidarabine) is a DNA polymerase inhibitor that has demonstrated activity
against herpes simplex virus type I (HSV-1) infections, responsible for “cold sores” on
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