Antiviral Drugs - Drug Design and Discovery - page 404

Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Peptidomimetic inhibitor of HIV protease.
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (i.e., NRTIs).
Administered : Orally, as two 300 mg tablets twice daily, together with ritonavir 100 mg twice daily
and with food.

24.2.5 V IRAL E NTRY I NHIBITORS
24.2.5.1 Enfuvirtide
Structure (Figure 24.8): 36-Amino acid peptide, corresponding to amino acid residues 643-678 of
the viral glycoprotein precursor gp160 (or amino acid residues 127-162 of the viral glycoprotein
gp41), DP-178, pentafuside, T-20, Fuzeon ® .
Activity spectrum : HIV-1.
Mechanism of action : Inhibits virus-cell fusion, through a coil-coil interaction with its homologous
region in gp41 (Figure 24.9).
Principal indication(s) : HIV infection, in combination with other anti-HIV agents; generally used
for salvage therapy in highly drug-experienced patients.
Administered : By subcutaneous injection, twice daily at a dose of 90 mg.

24.3 ANTI-HBV COMPOUNDS

24.3.1 L AMIVUDINE
Lamivudine (Figure 24.1) is used in the treatment of both HIV and HBV infections; for the former
at an oral dose of 300 mg/day, for the latter at an oral dose of 100 mg/day.

24.3.2 A DEFOVIR D IPIVOXIL
Structure (Figure 24.10): Bis(pivaloyloxymethyl)ester of 9-(2-phosphonylmethoxyethyl)adenine, or
bis(POM)PMEA, Hepsera ® .
Activity spectrum : HBV, HIV, and other retroviruses, and, to a lesser extent, also herpesviruses
(HSV, CMV, etc.).

Membrane
spanning
region

Fusion
peptide

Leucine zipper
region

152 amino acids

NH 2 CC COOH

517 532 558 595 643 678 689 710

DP-107 DP-178

YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF

Enfuvirtide

FIGURE 24.8 Structure of enfuvirtide, a 36-amino acid fragment of the viral glycoprotein precursor gp 160.