SLiM-binding pockets: an attractive target for broad-spectrum antivirals

Leandro Simonetti; Jakob Nilsson; Gerald McInerney; Ylva Ivarsson; Norman E. Davey

doi:10.1016/j.tibs.2022.12.004

SLiM-binding pockets: an attractive target for broad-spectrum antivirals

Leandro Simonetti
, Jakob Nilsson
, Gerald McInerney
, Ylva Ivarsson
, Norman E. Davey^*

^*Corresponding author for this work

Research output: Contribution to journal › Review › peer-review

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Abstract

Short linear motif (SLiM)-mediated interactions offer a unique strategy for viral intervention due to their compact interfaces, ease of convergent evolution, and key functional roles. Consequently, many viruses extensively mimic host SLiMs to hijack or deregulate cellular pathways and the same motif-binding pocket is often targeted by numerous unrelated viruses. A toolkit of therapeutics targeting commonly mimicked SLiMs could provide prophylactic and therapeutic broad-spectrum antivirals and vastly improve our ability to treat ongoing and future viral outbreaks. In this opinion article, we discuss the therapeutic relevance of SLiMs, advocating their suitability as targets for broad-spectrum antiviral inhibitors.

Original language	English
Journal	Trends in Biochemical Sciences
Volume	48
Issue number	5
Pages (from-to)	420-427
ISSN	0968-0004
DOIs	https://doi.org/10.1016/j.tibs.2022.12.004
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Funding

We thank the SLiM biology community for their valuable discussions on this topic over the past years and Camilla Rega for critically reading the final manuscript. None are declared.

Keywords

inhibitors
protein–protein interactions
short linear motifs
viral outbreak preparedness
viruses

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10.1016/j.tibs.2022.12.004Licence: CC BY

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Cite this

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abstract = "Short linear motif (SLiM)-mediated interactions offer a unique strategy for viral intervention due to their compact interfaces, ease of convergent evolution, and key functional roles. Consequently, many viruses extensively mimic host SLiMs to hijack or deregulate cellular pathways and the same motif-binding pocket is often targeted by numerous unrelated viruses. A toolkit of therapeutics targeting commonly mimicked SLiMs could provide prophylactic and therapeutic broad-spectrum antivirals and vastly improve our ability to treat ongoing and future viral outbreaks. In this opinion article, we discuss the therapeutic relevance of SLiMs, advocating their suitability as targets for broad-spectrum antiviral inhibitors.",

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AU - Davey, Norman E.

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AB - Short linear motif (SLiM)-mediated interactions offer a unique strategy for viral intervention due to their compact interfaces, ease of convergent evolution, and key functional roles. Consequently, many viruses extensively mimic host SLiMs to hijack or deregulate cellular pathways and the same motif-binding pocket is often targeted by numerous unrelated viruses. A toolkit of therapeutics targeting commonly mimicked SLiMs could provide prophylactic and therapeutic broad-spectrum antivirals and vastly improve our ability to treat ongoing and future viral outbreaks. In this opinion article, we discuss the therapeutic relevance of SLiMs, advocating their suitability as targets for broad-spectrum antiviral inhibitors.

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KW - protein–protein interactions

KW - short linear motifs

KW - viral outbreak preparedness

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