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

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

Journal: Trends in biochemical sciences 2023;48(5):420-427

PMID: 36623987

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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.

Address: Department of Chemistry - BMC, Husargatan 3, 751 23 Uppsala, Sweden.; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, Blegdamsvej 3B, 2200 Copenhagen, Denmark.; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2022.12.004

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https://linkinghub.elsevier.com/retrieve/pii/S0968...

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-FHL1-1

MeSH Terms: Antiviral Agents, Amino Acid Motifs