PXD035805-1

PXD035805 is an original dataset announced via ProteomeXchange.

Title	A comprehensive SARS-CoV-2-human protein-protein interactome network that can identify pathobiology and host-targeting therapies for COVID-19
Description	Physical interactions between viral and host proteins are responsible for almost all aspects of the viral life cycle and the host’s immune response. Studying viral-host protein-protein interactions is thus crucial for identifying strategies for treatment and prevention of viral infection. Here, we use high-throughput yeast two-hybrid and affinity purification followed by mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of both binary and co-complex interactions. We report a total of 739 high-confidence interactions, showing the highest overlap of interaction partners among published datasets as well as the highest overlap with genes differentially expressed in samples (such as upper airway and bronchial epithelial cells) from patients with SARS-CoV-2 infection. Showcasing the utility of our network, we describe a novel interaction between the viral accessory protein ORF3a and the host zinc finger transcription factor ZNF579 to illustrate a SARS-CoV-2 factor mediating a direct impact on host transcription. Leveraging our interactome, we performed network-based drug screens for over 2,900 FDA-approved/investigational drugs and obtained a curated list of 23 drugs that had significant network proximities to SARS-CoV-2 host factors, one of which, carvedilol, showed promising antiviral properties. We performed electronic health record-based validation using two independent large-scale, longitudinal COVID-19 patient databases and found that carvedilol usage was associated with a significantly lowered probability (17%-20%, P < 0.001) of obtaining a SARS-CoV-2 positive test after adjusting various confounding factors. Carvedilol additionally showed anti-viral activity against SARS-CoV-2 in a human lung epithelial cell line [(half maximal effective concentration (EC 50 ) value of 4.1 µM]), suggesting a mechanism for its beneficial effect in COVID-19. Our study demonstrates the value of large-scale network systems biology approaches for extracting biological insight from complex biological processes.
HostingRepository	PRIDE
AnnounceDate	2023-03-11
AnnouncementXML	Submission_2023-03-10_23:45:37.934.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ShagunGupta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: 2697049;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-04 07:57:16	ID requested
⏵ 1	2023-03-10 23:45:38	announced
2	2023-11-14 08:38:43	announced	2023-11-14: Updated project metadata.

Zhou Y, Liu Y, Gupta S, Paramo MI, Hou Y, Mao C, Luo Y, Judd J, Wierbowski S, Bertolotti M, Nerkar M, Jehi L, Drayman N, Nicolaescu V, Gula H, Tay S, Randall G, Wang P, Lis JT, Feschotte C, Erzurum SC, Cheng F, Yu H, A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nat Biotechnol, 41(1):128-139(2023) [pubmed]

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: Y2H,SARS-CoV-2, TMT, Human, IP-MS, virus pathobiology

HaiyuanYu
contact affiliation	Weill Institute for Cell and Molecular Biology, Department of Computational Biology, Cornell University
contact email	haiyuan.yu@cornell.edu
lab head
ShagunGupta
contact affiliation	Cornell University
contact email	sg2369@cornell.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD035805

PRIDE project URI

• PRIDE
  1. PXD035805
     1. Label: PRIDE project
     2. Name: A comprehensive SARS-CoV-2-human protein-protein interactome network that can identify pathobiology and host-targeting therapies for COVID-19