Acyclovir mechanism

(acycloguanosine) is the prototypic antiherpetic therapeutic agent. It has a greater specificity than vidarabine against herpesviruses. Herpes simplex virus (HSV) Types 1 and 2, varicella-zoster virus (VZV), and some Epstein-Barr virus–mediated infections are sensitive to acyclovir. It is the treatment of choice in HSV encephalitis and is more efficacious than vidarabine at increasing the rate of survival. The most common use of acyclovir is in therapy for genital herpes infections. It is also given prophylactically to seropositive patients before bone marrow and after heart transplants to protect such individuals during posttransplant immunosuppressive treatments. It is monophosphorylated in the cell by the herpes virus–encoded enzyme, thymidine kinase Therefore, virus-infected cells are most susceptible. The monophosphate analog is converted to the di- and triphosphate forms by the host cells. Acyclovir triphosphate competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase and is itself incorporated into the viral DNA, causing premature DNA-chain termination Irreversible binding of the acyclovir-containing template primer to viral DNA polymerase inactivates the enzyme. The drug is less effective against the host enzyme. Because of its short half-life, oral administration requires multiple daily doses of acyclovir.Renal excretion is the major route of elimination of acyclovir