PT  - JOURNAL ARTICLE
AU  - Filip Mihalic
AU  - Leandro Simonetti
AU  - Girolamo Giudice
AU  - Marie Rubin Sander
AU  - Richard Lindqvist
AU  - Marie Berit Akprioro Peters
AU  - Caroline Benz
AU  - Eszter Kassa
AU  - Dilip Badgujar
AU  - Raviteja Inturi
AU  - Muhammad Ali
AU  - Izabella Krystkowiak
AU  - Ahmed Sayadi
AU  - Eva Andersson
AU  - Hanna Aronsson
AU  - Ola Söderberg
AU  - Doreen Dobritzsch
AU  - Evangelia Petsalaki
AU  - Anna K Överby
AU  - Per Jemth
AU  - Norman E. Davey
AU  - Ylva Ivarsson
TI  - Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs
AID  - 10.1101/2022.06.19.496705
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.19.496705
4099  - http://biorxiv.org/content/early/2022/06/19/2022.06.19.496705.short
4100  - http://biorxiv.org/content/early/2022/06/19/2022.06.19.496705.full
AB  - Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1,712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.Competing Interest StatementThe authors have declared no competing interest.