polymerase activities. The NNRTIs include nevirapine (9.22), delavirdine (9.23), and
efavirenz (9.24).
The third and most recent class of antiretroviral agent is the protease inhibitor.
During the late stage of the HIV growth cycle, precursor macromolecules are cleaved
into structural proteins that constitute an integral part of the mature HIV virion particle.
This cleavage process is catalyzed by a protease enzyme; inhibition of this enzyme
renders the viral particle non-infectious, preventing the ongoing wave of HIV infection.
HIV protease is a dimer in which each monomer has an active site containing one or
two aspartate residues. Using crystallographic three-dimensional data and molecular
modeling studies, drugs have been designed to be transition-state mimetics, aligning at
the enzyme active site. Some of the successful protease inhibitors include saquinavir
(9.25), ritonavir (9.26), indinavir (9.27), nelfinavir (9.28), and amprenavir (9.29).
In the clinical setting, the combination of at least two antiretroviral agents is now
recommended to ensure enhanced potency and to delay the emergence of resistance.
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