Antiviral Drugs - Drug Design and Discovery - page 411

24.4.2.2 Valganciclovir
Structure (Figure 24.14): l-Valine ester of ganciclovir (VGCV), Valcyte ® .
Activity spectrum : As for GCV.
Mechanism of action : Serves as oral prodrug of GCV, and then acts as described for GCV. Principal
indication(s) : CMV infections. Oral valganciclovir is expected to replace intravenous ganciclovir in
both the therapy and prevention of CMV infections.
Administered : Orally at 900 mg/day (two 450 mg tablets daily) for maintenance therapy (900 mg
twice daily for induction therapy).

24.4.2.3 Foscarnet
Structure (Figure 24.14): Trisodium phosphonoformate, foscarnet sodium, Foscavir ® .
Activity spectrum : Herpesviruses (HSV-1, HSV-2, VZV, CMV, etc.) and also HIV.
Mechanism of action : Pyrophosphate analog, interferes with the binding of the pyrophosphate (diphos-
phate) to its binding site of the viral DNA polymerase, during the process of DNA polymerization.
Principal indication(s) : CMV retinitis in AIDS patients, and mucocutaneous acyclovir-resistant
(viral TK-dei cient) HSV and VZV infections in immunocompromised patients.
Administered : Intravenously at 180 mg/kg/day (3 × 60 mg/kg, every 8 h) for induction therapy of
CMV retinitis; intravenously at 120 mg/kg/day (3 × 40 mg/kg, every 8 h) for maintenance therapy
of CMV retinitis and for therapy of acyclovir-resistant mucocutaneous HSV or VZV infections in
immunocompromised patients. Dose adjustments for changes in renal function are imperative.

24.4.2.4 Cidofovir
Structure (Figure 24.14): ( S )-1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC),
(CDV), Vistide ® .
Activity spectrum : Herpesviruses (HSV-1, HSV-2, VZV, CMV, etc.), papilloma-, polyoma-, adeno-,
and poxviruses.
Mechanism of action : Targeted at the viral DNA polymerase, acts as a chain terminator, following
intracellular phosphorylation to the diphosphate form, and incorporation at the 3 -end of the viral

DNA chain (two sequential incorporations needed for chain termination in the case of CMV DNA
synthesis) (Figure 24.15).
Principal indications(s) : Ofi cially licensed for the treatment of CMV retinitis in AIDS patients.
Also shown to be effective in the treatment of acyclovir-resistant (viral TK-dei cient) HSV infections,
recurrent genital herpes, genital warts, CIN-III (cervical intraepithelial neoplasia grade III), laryn-
geal and cutaneous papillomatous lesions, molluscum contagiosum lesions, orf lesions, adenovirus
infections, and progressive multifocal leukoencephalopathy (PML).
Administered : Intravenously (Vistide) at 5 mg/kg/week during the i rst 2 weeks, then 5 mg/kg every
other week, with sufi cient hydration and under cover of probenecid to prevent nephrotoxicity. It can
also be administered topically as a 1% gel or cream.

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24.4.2.5 Fomivirsen
Structure (Figure 24.14): Antisense oligodeoxynucleotide composed of 21 phosphorothioate-linked
nucleosides, ISIS 2922, Vitravene ® .
Activity spectrum : CMV.
Mechanism of action : Being complementary in base sequence, it hybridizes with, and thus blocks
expression (translation) of, the CMV immediate and early 2 (IE2) mRNA.
Principal indication(s) : CMV retinitis (in AIDS patients).
Administered : Intraocularly (intravitreally).