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Pathway Description

Foscarnet Action Pathway

Homo sapiens

Category:

Metabolite Pathway

Sub-Category:

Drug Action

Created: 2023-02-27

Last Updated: 2023-10-25

Foscarnet is an antiviral used to treat CMV, HIV, and HSV infections. Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Foscarnet inhibits the activity of DNA polymerase by competing with its substrate dGTP. Less viral proteins produced, fewer viruses can form.

References

Foscarnet Pathway References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.

Pubmed: 17139284

Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.

Pubmed: 17016423

Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. doi: 10.1016/j.jviromet.2006.11.039. Epub 2007 Jan 2.

Pubmed: 17197042

Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88.

Pubmed: 17926642

Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. doi: 10.1128/JVI.80.3.1440-1450.2006.

Pubmed: 16415021

Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.

Pubmed: 29126136

Highlighted elements will appear in red.

Highlight Compounds

	dGTP
	Foscarnet

Highlight Proteins

	ABC transporter, substrate-binding lipoprotein
	DNA polymerase catalytic subunit

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