A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
12
02
2022
accepted:
15
08
2022
pubmed:
11
10
2022
medline:
21
1
2023
entrez:
10
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36217030
doi: 10.1038/s41587-022-01474-0
pii: 10.1038/s41587-022-01474-0
pmc: PMC9851973
mid: NIHMS1846738
doi:
Substances chimiques
Viral Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128-139Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG009391
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG074001
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL060917
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115398
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG073323
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG066707
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124559
Pays : United States
Organisme : NIGMS NIH HHS
ID : RM1 GM139738
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG009393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R37 HL060917
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122550
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG076448
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125639
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130885
Pays : United States
Organisme : NHGRI NIH HHS
ID : F31 HG010820
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM013337
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
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