{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou Y"],"funding":["NCATS NIH HHS","NIA NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","NHGRI NIH HHS","NLM NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health","NIGMS NIH HHS"],"pagination":["128-139"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9851973"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(1)"],"pubmed_abstract":["Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients. We identify an interaction between the viral protein ORF3a and the human transcription factor ZNF579, illustrating a direct viral impact on host transcription. We perform network-based screens of >2,900 FDA-approved or investigational drugs and identify 23 with significant network proximity to SARS-CoV-2 host factors. One of these drugs, carvedilol, shows clinical benefits for COVID-19 patients in an electronic health records analysis and antiviral properties in a human lung cell line infected with SARS-CoV-2. Our study demonstrates the value of network systems biology to understand human-virus interactions and provides hits for further research on COVID-19 therapeutics."],"journal":["Nature biotechnology"],"pubmed_title":["A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets."],"pmcid":["PMC9851973"],"funding_grant_id":["R01 DK115398","R01 GM130885","F31 HG010820","R01 LM013337","UM1 HG009393","UL1 TR001422","R01 AG066707","R01 AG076448","RM1GM139738","U01 HG009391","R01 HL060917","R56 AG074001","R35 GM122550","U01 AG073323","R37 HL060917","RM1 GM139738","R01 GM125639","R01GM124559","R01 GM124559"],"pubmed_authors":["Gula H","Gupta S","Cheng F","Wierbowski S","Nerkar M","Nicolaescu V","Zhou Y","Hou Y","Bertolotti M","Feschotte C","Paramo MI","Jehi L","Yu H","Liu Y","Tay S","Judd J","Wang P","Mao C","Erzurum SC","Lis JT","Luo Y","Drayman N","Randall G"],"additional_accession":[]},"is_claimable":false,"name":"A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.","description":"Studying viral-host protein-protein interactions can facilitate the discovery of therapies for viral infection. We use high-throughput yeast two-hybrid experiments and mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of 739 high-confidence binary and co-complex interactions, validating 218 known SARS-CoV-2 host factors and revealing 361 novel ones. Our results show the highest overlap of interaction partners between published datasets and of genes differentially expressed in samples from COVID-19 patients. We identify an interaction between the viral protein ORF3a and the human transcription factor ZNF579, illustrating a direct viral impact on host transcription. We perform network-based screens of >2,900 FDA-approved or investigational drugs and identify 23 with significant network proximity to SARS-CoV-2 host factors. One of these drugs, carvedilol, shows clinical benefits for COVID-19 patients in an electronic health records analysis and antiviral properties in a human lung cell line infected with SARS-CoV-2. Our study demonstrates the value of network systems biology to understand human-virus interactions and provides hits for further research on COVID-19 therapeutics.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-28T16:46:17.243Z","creation":"2025-02-19T03:00:29.953Z"},"accession":"S-EPMC9851973","cross_references":{"pubmed":["36217030"],"doi":["10.1038/s41587-022-01474-0"]}}