Description
Foscarnet is an antiviral compound that inhibits reverse transcriptase of HIV-1 and DNA polymerase of other viruses, including CMV and HSV. Inhibition of these enzymes prevents DNA synthesis and viral replication. Foscarnet chelates with metal ions and also mimics the pyrophosphate leaving group in DNA polymerase, inducing a closed/un-translocated conformational state. Additionally, foscarnet inhibits type II inorganic phosphate (Pi) transporters in smooth muscle cells, inhibiting Ca2+ deposition and vascular calcification.
References
Zahn KE, Tchesnokov EP, Götte M, et al. Phosphonoformic acid inhibits viral replication by trapping the closed form of the DNA polymerase. J Biol Chem. 2011 Jul 15;286(28):25246-55. PMID: 21566148.
Villa-Bellosta R, Sorribas V. Phosphonoformic acid prevents vascular smooth muscle cell calcification by inhibiting calcium-phosphate deposition. Arterioscler Thromb Vasc Biol. 2009 May;29(5):761-6. PMID: 19213941.
Marchand B, Tchesnokov EP, Götte M. The pyrophosphate analogue foscarnet traps the pre-translocational state of HIV-1 reverse transcriptase in a Brownian ratchet model of polymerase translocation. J Biol Chem. 2007 Feb 2;282(5):3337-46. PMID: 17145704.
Morfin F, Thouvenot D. Herpes simplex virus resistance to antiviral drugs. J Clin Virol. 2003 Jan;26(1):29-37. PMID: 12589832.
Hardy WD. Foscarnet treatment of acyclovir-resistant herpes simplex virus infection in patients with acquired immunodeficiency syndrome: preliminary results of a controlled, randomized, regimen-comparative trial. Am J Med. 1992 Feb 14;92(2A):30S-35S. PMID: 1531285.
