The potency of acyclovir can be markedly different in different cell types.
Acyclovir is an acyclic guanine analog with a considerable activity against herpes simplex viruses. We studied the antiherpetic activity of acyclovir in macrophages and fibroblast cell lines. Utilising a plaque reduction assay we found that acyclovir potently inhibited the HSV-1 replication in macrophages (EC50) = 0.0025 microM) compared to Vero (EC50 = 8.5 microM) and MRC-5 (EC50 = 3.3 microM) cells. The cytotoxicity of acyclovir was not detected at concentrations < or = 20 microM, thus the selective index in macrophages was >8000. This marked difference in antiherpetic activity between macrophages and fibroblasts was not observed with Foscarnet and PMEA. We suggest that this potent antiviral effect of acyclovir is mainly due to a proficient phosphorylation of the drug and/or a favourable dGTP/acyclovir triphosphate ratio in macrophage cells.
Brand
G
G
Institute of Toxicologic Hygienic and Environmental Science, G. Fornaini University of Urbino, Italy. brandi@bio.uniurb.it
Schiavano
G F
GF
Balestra
E
E
Tavazzi
B
B
Perno
C F
CF
Magnani
M
M
D000179:Acrylates / Q000494:pharmacology; D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured / Q000821:virology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000821:virology; D017245:Foscarnet / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008264:Macrophages / Q000821:virology; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000494:pharmacology; D014709:Vero Cells / Q000821:virology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000179:Acrylates; D000998:Antiviral Agents; D011108:Polymers; C413485:poly(2-methoxyethylacrylate); D017245:Foscarnet; D000212:Acyclovir