Biochemical principles and inhibitors to interfere with viral capping pathways

Current Opinion in Virology
E Decroly, Bruno Canard

Abstract

Messenger RNAs are decorated by a cap structure, which is essential for their translation into proteins. Many viruses have developed strategies in order to cap their mRNAs. The cap is either synthetized by a subset of viral or cellular enzymes, or stolen from capped cellular mRNAs by viral endonucleases ('cap-snatching'). Reverse genetic studies provide evidence that inhibition of viral enzymes belonging to the capping pathway leads to inhibition of virus replication. The replication defect results from reduced protein synthesis as well as from detection of incompletely capped RNAs by cellular innate immunity sensors. Thus, it is now admitted that capping enzymes are validated antiviral targets, as their inhibition will support an antiviral response in addition to the attenuation of viral mRNA translation. In this review, we describe the different viral enzymes involved in mRNA capping together with relevant inhibitors, and their biochemical features useful in inhibitor discovery.

References

Feb 26, 2016·MBio·Paul SmithStewart Shuman

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Citations

Apr 7, 2018·Wiley Interdisciplinary Reviews. RNA·Nikolay E Shirokikh, Thomas Preiss
Nov 7, 2019·Wiley Interdisciplinary Reviews. RNA·Rachel Netzband, Cara T Pager
Jun 5, 2019·Nature Structural & Molecular Biology·Aartjan J W Te Velthuis
Apr 30, 2019·Wiley Interdisciplinary Reviews. RNA·Shaun T CrossJeffrey Wilusz
Jun 22, 2020·European Journal of Medicinal Chemistry·Rostom Ahmed-BelkacemFrançoise Debart
Feb 24, 2021·RNA Biology·Lukasz MarkiewiczPawel J Sikorski
Mar 12, 2021·Nucleic Acids Research·Lisa WeixlerRoko Žaja
Apr 21, 2021·SLAS Discovery·Aliakbar Khalili YazdiMasoud Vedadi
May 21, 2021·Journal of Virology·Pavel DostalikEvzen Boura
Apr 9, 2019·Current Opinion in Plant Biology·Kristiina Mäkinen, Swarnalok De

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Methods Mentioned

BETA
GTase
GTases
X-ray
protein

Software Mentioned

ANTIVIRALS

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