Design and testing of antiviral compounds

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Abstract
The search for antiviral drugs began in earnest in the 1950s but this was directed mainly by chance, with little or no scientific basis. Early successes included the use of methisazone (Marboran) for the prophylaxis of smallpox and the use of idoxuridine (IUDR) for the treatment of herpes keratitis. It was soon realized that viral DNA or RNA replication involved virus-specified enzymes which provided potential targets for intervention, and the main emphasis in drug development became centred on nucleoside analogues. Several active drugs were identified, mainly against herpesviruses, but because of cellular toxicity their clinical usefulness was limited. A major breakthrough came in the late 1970s with the discovery of acyclovir (ACV; see reference 2), the most effective and least toxic antiviral drug developed so far. More recently a drug related to acyclovir, ganciclovir, has emerged which is effective against cytomegalovirus (CMV; see reference 3). The nucleoside analogue azidothymidine (AZT) has been developed for the treatment of human immunodeficiency virus (HIV) infections

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