Herpes viruses cidofovir

Cidofovir (Figure 24.4) is an antiviral cytidine nucleotide analog with inhibitory activity against HCMV and other herpes viruses. Cidofovir is first converted to an active diphosphate form by cellular enzymes. Antiviral effects of cidofovir are due to inhibition of viral DNA polymerase by the diphosphate metabolite (Neyts and De Clercq, 1994 Plosker and Noble, 1999 Scholar and Pratt, 2000). The diphosphate probably interacts with DNA polymerase either as an alternate substrate (incorporation at the 3 end or within the interior of the DNA chain) or as a competitive inhibitor (with respect to the normal substrate dCTP). Cidofovir inhibits HCMV DNA synthesis at intracellular concentrations 1000-fold lower than are required to inhibit cellular DNA synthesis (Neyts and De Clercq, 1994). For HSV-1 and HSV-2 corresponding concentrations are at least 50-fold lower. 

Viruses other than HIV may be treated by blocking the action of nucleotide polymerases. Acyclovir (Zovirax, 6.56) and famciclovir (Famvir, 6.57) are used against various herpes viruses (Figure 6.22). Cidofovir (Vistide, 6.58) is active against cytomegaloviral retinitis in patients who are infected with HIV. Ribavirin (Rebetol, 6.59) is approved for use against hepatitis C virus. 

Azetidine 25 has shown promising anti-human cytomegalovirus (HCMV) activity. Human cytomegalovirus is a ubiquitous member of the herpes virus family. The EGso value obtained for this compound has been found to be similar to that of the standard reference compound ganciclovir and slightly better than that of cidofovir... 

Cidofovir is an acyclic nucleotide analogue of the monophosphate of cytosine. When phosphoiylated by host cellular enzymes, the active compound cidofovir diphosphate has broad activity against the herpes viruses, including CMV, HSV 1 and 2, VZV, Epstein-Barr virus, and the BK polyomavirus. Cidofovir has primarily been used in the treatment of CMV retinitis in patients who have failed treatment with ganciclovir or foscarnet and in acyclovir-resistant herpes simplex infections. More recently, there is also a growing experience with the use of this medication in kidney transplant patients who have BK virus-associated nephropathy [31], although this interest has been dampened by significant toxicity and only modest clinical activity [32]... 

Hitchcock MJM, Jaffe HS, Martin JC, Stagg RJ. Cidofovir, a new agent with potent anti-herpes virus activity. Antiviral Chem Chemother 1996 7 115-127. 

Herpesviruses are associated with a broad spectrum of diseases, for example, cold sores, viral encephalitis, and genital infections, the latter being a hazard to the newborn during parturition. The drugs that are effective against these viruses exert their actions during the acute phase of viral infections, and are without effect in the latent phase. Two new anti-herpes agents are penciclovir and cidofovir. 

Keywords Encephalitis Herpes simplex virus type 1 Varicella zoster virus Cytomegalovirus West Nile virus Acyclovir Valacyclovir Ganciclovir Cidofovir Famciclovir Foscamet Latencyneurological disorders Fifecycle... 

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