Epstein-Barr virus acyclovir

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV) is clinically useful in the treatment of infections caused by several members of the herpes virus (e.g., herpes simplex, varicella zoster and Epstein-Barr virus [2,38,39]). An enzyme coded for by the virus phosphorylates ACV to a monophosphate intermediate. This species in turn undergoes further phosphorylation to a triphosphate with the aid of normal cell enzymes. Then, ACV triphosphate inhibits the herpes virus DNA... 

As it is evident from the chemical strnctnre, acyclovir looks like a nucleoside analog of gnanosine in side chain of which, instead of the traditional cyclic sugar residue a 2-hydrox-yethoxymethyl acyclic side chain is present. Acyclovir possesses antiviral activity with respect to types 1 and 2 of herpes simplex, shingles vims, Epstein-Barr virus, and cytomegalovirns. 

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. 

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. 

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. 

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]... 

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. 

Acyclovir s clinical use is limited to herpesviruses. Acyclovir is most active against HSV-1, approximately half as active against HS V-2, a tenth as potent against vaiicella-zoster virus (VZV) and Epstein-Barr virus (EBV), and least active against cytomegalovirus (CMV) and human herpesvirus (HHV-6). Uninfected mammalian cells generally are unaffected by high acyclovir concentrations. 

Acyclovir is widely used to inhibit several herpes viruses, particularly HSV-1 and HSV-2 [32-34], It is also used to treat varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The inhibitory activity of acyclovir is highly selective. Thus, acyclovir is a first line antivirial drug. 

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