Antiviral Drugs - Drug Design and Discovery - page 406

24.3.3 E NTECAVIR
Structure (Figure 24.10): 2-Amino-1,9-dihydro-9-[( 1S,3R,4S )-4-hydroxy-3-(hydroxymethyl)-2-
methylenecyclopentyl]-6 H -purin-6-one, monohydrate, Baraclude ® .
Activity spectrum : HBV.
Mechanism of action : Targeted at HBV RT, following intracellular phosphorylation to its
triphosphate.
Principal indication(s) : Chronic hepatitis B (either HBeAg-positive or -negative patients).
Administered : Orally as 0.5 mg tablet once daily (1 mg once daily for lamivudine-resistant).

24.3.4 T ELBIVUDINE
Structure (Figure 24.10): 1-((2 S ,4 R ,5 S )-4-Hydroxy-5-hydroxymethyltetrahydrofuran-2-y1)-5-methyl-
1 H -pyrimidine-2,4-dione, or 1-(2-deoxy-

β -l-ribofuranosyl)-5-methyluracil, Tyzeka ® .

Activity spectrum : HBV.
Mechanism of action : Targeted at HBV RT, following intracellular phosphorylation to its triphosphate.
Principal indication(s) : Chronic hepatitis B (HBeAg-positive or -negative).
Administered : Orally as a 600 mg tablet once daily.

24.4 ANTIHERPESVIRUS COMPOUNDS

24.4.1 HSV AND VZV I NHIBITORS

24.4.1.1 Acyclovir
Structure (Figure 24.11): 9-(2-Hydroxyethoxymethyl)guanine, acycloguanosine (ACG), acyclovir,
aciclovir (ACV), Zovirax ® .
Activity spectrum : HSV (types 1 and 2) and VZV.
Mechanism of action : Targeted at the viral DNA polymerase, acts as a chain terminator, follow-
ing intracellular phosphorylation to ACV triphosphate and incorporation of ACV monophosphate
at the 3 -end of the viral DNA chain (Figure 24.12). The i rst phosphorylation step is catalyzed by

the virus-encoded thymidine kinase (TK), which explains the specii city of acyclovir for HSV-1,
HSV-2, and VZV.
Principal indication(s) : Mucosal, cutaneous, and systemic HSV-1 and HSV-2 infections (including
herpetic keratitis, herpetic encephalitis, genital herpes, neonatal herpes, and herpes labialis) and
VZV infections (including varicella and herpes zoster).
Administered : Orally at 1000 mg/day (i ve 200 mg tablets [genital herpes]) or 4000 mg/day (four times
i ve 200 mg tablets [herpes zoster]), topically as a 3% ophthalmic cream (herpetic keratitis) or
5% cream (herpes labialis), or intravenously at 30 mg/kg/day (herpetic encephalitis, and other severe
HSV or VZV infections).

′

24.4.1.2 Valaciclovir
Structure (Figure 24.11): l-Valine ester of acyclovir (VACV), Zelitrex ® , Valtrex ® .
Activity spectrum : As for acyclovir.
Mechanism of action : Serves as oral prodrug of acyclovir, and then acts as described for acyclovir.
Principal indication(s) : HSV and VZV infections that can be approached by oral therapy (i.e.,
genital herpes, herpes zoster). Also used in the prophylaxis of CMV infections in transplant
recipients.
Administered : Orally at 1000 mg/day (two 500 mg tablets [genital herpes]) up to 3000 mg/day
(three times two 500 mg tablets [herpes zoster]).