Nucleoside analogues for the treatment of coronavirus infections

Andrea J Pruijssers, Mark R Denison, Andrea J Pruijssers, Mark R Denison

Abstract

Recent outbreaks of SARS-Coronavirus and MERS-Coronavirus (CoV) have heightened awareness about the lack of vaccines or antiviral compounds approved for prevention or treatment of human or potential zoonotic CoVs. Anti-CoV drug development has long been challenged by the activity of a 3' to 5' proofreading exoribonuclease unique to CoVs. Recently, a promising nucleoside analogue with broad-spectrum activity against CoVs has been identified. This review will discuss progress made in the development of antiviral nucleoside and nucleotide analogues targeting viral RNA synthesis as effective therapeutics against CoV infections and propose promising strategies for combination therapy.

Copyright © 2019. Published by Elsevier B.V.

Figures

Figure 1
Figure 1
Mechanisms of inhibition by nucleoside and nucleotide analogues. Schematic representation illustrates normal replication by the RdRp (blue sphere), premature chain termination caused by an obligate chain terminator, reduced replication fidelity due to mutagen incorporation, and depletion of pools of naturally occurring nucleotides.

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