Biomedical Engineering Reference
In-Depth Information
N
O
O
N
O
N
O
N
N
N
S
O
N
N
O
O
O
O
O
O
O
O
P
O
O
O
N
Atazanavir
Fosamprenavir
O
N
O
O
S
N
O
O
H
N
O
H
O
N
N
H
O
H
N
Indinavir
Nelfinavir
O
S
N
O
O
N
O
O
O
N
N
H
O
N
H
N
N
O
O
O
S
Ritonavir
Lopinavir
N
H
O
O
O
O
O
N
S
H
H
O
N
N
N
F
H
O
F
F
O
N
O
O
Saquinavir
Tipranavir
FIGURE 11.9
Clinically approved HIV-1 protease inhibitors for the treatment of AIDS.
the viral enzymes and structural proteins, and it is absolutely indispensable for proper virion assem-
bly and maturation. For this reason it has been an important target for the discovery of anti-HIV
therapeutics, and indeed there are at least eight drugs in current clinical use whose antiviral mode
of action is by potent inhibition of the HIV protease (Figure 11.9).
One of the major driving forces behind the rapid progress in the identii cation of HIV protease
inhibitors to combat AIDS has been the intense investigation of the structure of the enzyme, par-
ticularly in complex with a number of different inhibitors. HIV-1 PR is a dimer comprised of two
