Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents. Many interactions between viral and host proteins are mediated by short peptide motifs. Here, using a phage-based viral peptide library, the authors identify 269 peptide-based interactions for 18 coronaviruses, including an interaction between SARS-CoV-2 N and G3BP1/2 that affects stress granules.
【저자키워드】 Intrinsically disordered proteins, Protein-protein interaction networks, 【초록키워드】 Coronaviruses, coronavirus, Antiviral, SARS-COV-2 infection, peptide, Protein, nucleocapsid, viral replication, Virus-host interactions, Factors, molecular, stress granules, inhibitor, information, interactions, cellular, Interaction, motifs, Support, reagents, host protein, SARS-CoV-2 N, motif, Host, Affect, approach, identify, coronavirus strain, peptide-based, provide, translated, disrupt, disrupting, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, Protein, mechanism, Interaction, motif, reveal,