Cytomegalovirus acyclovir

Foscarnet Inhibition of viral DNA polymerase and reverse transcriptase at the pyrophosphate-binding site Cytomegalovirus, acyclovir-resistant herpes simplex, acyciovir-resistant variceila-zoster 6... 

It is an acyclic guanosine analog which require triphosphorylation for activation prior to inhibition of viral DNA polymerase. It is active against cytomegalovirus (CMV), varicellazoster virus, Epstein-Barr virus and human herpes virus-8. It is almost 100 times more potent than acyclovir against CMV. 

For example, acyclovir with TI — 10 against herpes simplex virus is safer or more selective [9] than its derivative, ganciclovir (TI = 2-3 against cytomegalovirus) [10]. 

Acyclovir (Figure 49-2) is an acyclic guanosine derivative with clinical activity against HSV-1, HSV-2, and VZV, but it is approximately 10 times more potent against HSV-1 and HSV-2 than against VZV. In vitro activity against Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) is present but weaker. 

Soyasaponin I and II were studied in vitro against herpes simplex virus type I (HSV-1). Soyasaponin II was more potent than soyasaponin I in the reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. This activity was not due to the inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus [160]. Astragaloside II afforded almost 100% protection of T-lymphocytes in vitro against the cytophatic effects of HIV infection. However, the EC50 of ca. 2.5 x 105 molar was difficult to achieve in vivo [98],... 

The lack of effect of available nucleoside analogs on cytomegalovirus (CMV) infection led to the synthesis of the acyclovir analog, ganciclovir [gan SYE kloe ver] (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine, DHPG). It is currently available for treatment of cytomegalic retinitis in immunocompromised patients. 

Mode of action Like acyclovir, ganciclovir is activated through conversion to the nucleoside triphosphate by viral and cellular enzymes, the actual pathway depending on the virus. Cytomegalovirus is deficient in thymidine kinase, and therefore forms the triphosphate by another route. The nucleotide competitively inhibits viral DNA polymerase and can be incorporated into the DNA to decrease the rate of chain elongation. 

Acyclovir Metabolized to acyclovir triphosphate, which inhibits virai DNA polymerase Herpes simplex, varicella-zoster, cytomegalovirus 2-3... 

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

Ganciclovir is an acyclic guanine nucleotide analog with a structure similar to acyclovir but with an additional hydroxymethyl group on the acyclic side chain. It is inhibitory to all herpes viruses but is especially active against cytomegalovirus. 

Foscamet is used for the treatment of cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant herpes simplex virus (HSV) infections. It may also be beneficial in other types of CMV or HSV infections (Wagstaff and Bryson, 1994). 

Acyclovir is useful for treating infections caused by HSV, herpes zoster, and for VZV infections (Whitley and Roizman, 2001). Although HCMV is relatively resistant to acyclovir, some cytomegalovirus infections have responded marginally to large doses of acyclovir, and it seems to be effective for the prophylaxis of cytomegalovirus infections in immunocompromised patients. Epstein-Barr virus is not sensitive to acyclovir, and clinical infections do not respond to the drug. 

Wade JC, Hintz M, McGuffin R, Springmeyer SC, Connor JD, Meyers JD. Treatment of cytomegalovirus pneumonia with high-dose acyclovir. Am J Med 1982 73(lA) 249-56. 

Ganciclovir is an acyclic nucleoside analogue of guanine that is structurally similar to acyclovir, but is more effective in the treatment and prophylaxis of severe cytomegalovirus infection in immunocompromised hosts. Ganciclovir is myelotoxic, but has no significant nephrotoxicity [22]. It does, however, require dose adjustment for patients with reduced kidney function. 

Meyers JD, Reed EC, Shepp DH, et al. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. N Engl J Med 1988 318 70-75. 

Singh N, Yu VL, Mieles L, et al. High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. Ann Intern Med 1994 120 375-381. 

Foscamet is an antiviral agent that inhibits replication of all known herpes viruses, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV). It is indicated in the treatment of CMV retinitis in patients with AIDS treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients and as combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

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