Aciclovir (INN) (IPA: ) or acyclovir (USAN, former BAN) is a guanine analogue antiviral drug used most commonly for the treatment of herpes simplex virus infection. It is one of the most commonly-used antiviral drugs, and is most commonly marketed under the trade name Zovirax (GSK).

Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity. Pharmacologist Gertrude B. Elion was awarded the 1988 Nobel Prize in Medicine partly for the development of aciclovir.

Pharmacology

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Mechanism of action

Aciclovir differs from previous nucleoside analogues in that it contains only a partial nucleoside structure – the sugar ring is replaced by an open-chain structure. It is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase. Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.

More on [ Aciclovir ]

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