A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets.
Nat Biotechnol
; 2022 Oct 10.
Artigo
em Inglês
| MEDLINE | ID: covidwho-2237630
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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Assunto da revista:
Biotecnologia
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
S41587-022-01474-0
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