The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

Abstract

This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. As with the first paper, rather than providing a chronological account, we have chosen to examine particular examples of structural modifications made to nucleoside analogues that have proven fruitful as various antiviral, anticancer, and other therapeutics. The first review covered the more common, and in most cases, single modifications to the sugar and base moieties of the nucleoside scaffold. This paper focuses on more recent developments, especially nucleoside analogues that contain more than one modification to the nucleoside scaffold. We hope that these two articles will provide an informative historical perspective of some of the successfully designed analogues, as well as many candidate compounds that encountered obstacles.

Highlights

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  This is the second of two invited articles reviewing the development of nucleoside analogue antiviral drugs.

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  It is written for a target audience of virologists and other non-chemists, and for chemists unfamiliar with the field.

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  Numerous modifications have been made to the nucleoside scaffold in order to impart therapeutic benefits.

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  Current nucleoside analogues employ a combination approach, using multiple modifications to the scaffold.

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  We examine thought processes, progress in synthetic chemistry and results of antiviral testing that led to approved drugs.