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J Proteome Res ; 19(11): 4553-4566, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-974862

ABSTRACT

While the COVID-19 pandemic is causing important loss of life, knowledge of the effects of the causative SARS-CoV-2 virus on human cells is currently limited. Investigating protein-protein interactions (PPIs) between viral and host proteins can provide a better understanding of the mechanisms exploited by the virus and enable the identification of potential drug targets. We therefore performed an in-depth computational analysis of the interactome of SARS-CoV-2 and human proteins in infected HEK 293 cells published by Gordon et al. (Nature2020, 583, 459-468) to reveal processes that are potentially affected by the virus and putative protein binding sites. Specifically, we performed a set of network-based functional and sequence motif enrichment analyses on SARS-CoV-2-interacting human proteins and on PPI networks generated by supplementing viral-host PPIs with known interactions. Using a novel implementation of our GoNet algorithm, we identified 329 Gene Ontology terms for which the SARS-CoV-2-interacting human proteins are significantly clustered in PPI networks. Furthermore, we present a novel protein sequence motif discovery approach, LESMoN-Pro, that identified 9 amino acid motifs for which the associated proteins are clustered in PPI networks. Together, these results provide insights into the processes and sequence motifs that are putatively implicated in SARS-CoV-2 infection and could lead to potential therapeutic targets.


Subject(s)
Betacoronavirus , Coronavirus Infections , Host-Pathogen Interactions/genetics , Pandemics , Pneumonia, Viral , Protein Interaction Maps , Algorithms , Amino Acid Motifs , Betacoronavirus/chemistry , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Cluster Analysis , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Gene Ontology , HEK293 Cells , Humans , Molecular Sequence Annotation , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Maps/genetics , Protein Interaction Maps/physiology , Proteins/chemistry , Proteins/classification , Proteins/genetics , Proteins/metabolism , SARS-CoV-2 , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolism
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