Antiviral Drugs - Drug Design and Discovery - page 394

24.4.1.2 Valaciclovir.............................................................................................406
24.4.1.3 Penciclovir ..............................................................................................407
24.4.1.4 Famciclovir.............................................................................................407
24.4.1.5 Idoxuridine .............................................................................................408
24.4.1.6 Tril uridine .............................................................................................408
24.4.1.7 Brivudin..................................................................................................409
24.4.2 CMV Inhibitors...................................................................................................... 410
24.4.2.1 Ganciclovir ............................................................................................. 410
24.4.2.2 Valganciclovir......................................................................................... 411
24.4.2.3 Foscarnet ................................................................................................ 411
24.4.2.4 Cidofovir................................................................................................. 411
24.4.2.5 Fomivirsen.............................................................................................. 411
24.5 Anti-Inl uenzavirus Compounds (Including Ribavirin)...................................................... 412
24.5.1 Amantadine............................................................................................................ 412
24.5.2 Rimantadine........................................................................................................... 413
24.5.3 Zanamivir............................................................................................................... 413
24.5.4 Oseltamivir ............................................................................................................ 414
24.5.5 Ribavirin ................................................................................................................ 414
24.6 Current State of the Art ...................................................................................................... 415
24.7 Antiviral Agents in (Pre)Clinical Development.................................................................. 416
24.8 Appraisal of Clinical Utility ............................................................................................... 416
Further Readings............................................................................................................................ 417

24.1 INTRODUCTION
The antiviral drug armamentarium, at the end of 2006, comprises more than 40 compounds that
have been ofi cially approved for clinical use. Most of the approved drugs date from the last 5 to 10
years, and at least half of them are used for the treatment of human immunodei ciency virus (HIV)
infections. The other antiviral drugs that are currently available are primarily used for the treatment
of hepatitis B virus (HBV), herpesvirus (herpes simplex virus [HSV], varicella-zoster virus [VZV],
and cytomegalovirus [CMV]), inl uenza virus, respiratory syncytial virus (RSV), and hepatitis C
virus (HCV) infections.

24.2 ANTI-HIV COMPOUNDS

24.2.1 N UCLEOSIDE R EVERSE T RANSCRIPTASE I NHIBITORS (NRTI S )
24.2.1.1 Zidovudine
Structure (Figure 24.1): 3 -dideoxythymidine, azidothymidine (AZT), ZDV, Retrovir ® .

Activity spectrum : HIV (types 1 and 2).
Mechanism of action : Targeted at the reverse transcriptase (RT) of HIV, acts as a chain termina-
tor in the RT reaction, following intracellular phosphorylation of AZT 5

′ -Azido-2 ′ ,3 ′

′ -triphosphate, and, after

removal of the diphosphate group, incorporation of AZT 5 ′ -monophosphate at the 3 ′ -end of the viral

DNA chain (Figure 24.2).
Principal indication(s) : HIV infection, in combination with other anti-HIV agents (such as lamivudine
and abacavir).
Administered : Orally at 600 mg/day (two 300 mg tablets daily).