Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs

Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs

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Abstract Viruses mimic host short linear motifs pulsar apx pro vape (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 1712 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 makita rf1101 and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.