Mechanism of action of foscarnet against viral polymerases.
Foscarnet is a pyrophosphate analogue with activity against herpesviruses, human immunodeficiency virus (HIV), and other RNA and DNA viruses. Foscarnet and its analogues achieve their antiviral effects via inhibition of viral polymerases, with such inhibition not being dependent on activation or phosphorylation of the compounds by viral or cellular proteins. Current evidence indicates that foscarnet interferes with exchange of pyrophosphate from deoxynucleoside triphosphate during viral replication by binding to a site on the herpesvirus DNA polymerase or HIV reverse transcriptase. Reviewed herein are basic findings regarding the mechanism of action and antiviral activity of foscarnet and the related compound phosphonoacetic acid (PAA), as well as findings regarding potential mechanisms of viral resistance and interactions with other antiviral agents.
Crumpacker
C S
CS
Department of Infectious Diseases, Beth Israel Hospital, Boston, Massachusetts 02215.
D000998:Antiviral Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D017245:Foscarnet; D015774:Ganciclovir / Q000494:pharmacology; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D054303:HIV Reverse Transcriptase; D006564:Herpesviridae / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D017245:Foscarnet; D054303:HIV Reverse Transcriptase; D012321:DNA-Directed RNA Polymerases; D010746:Phosphonoacetic Acid; D015774:Ganciclovir