Evidence map›Paper›PMID 35677070›Full record

ArticleResearch square2022

A comprehensive SARS-CoV-2-human protein-protein interactome network identifies pathobiology and host-targeting therapies for COVID-19.

Yadi Zhou, Yuan Liu, Shagun Gupta, Mauricio I Paramo, Yuan Hou, Chengsheng Mao, Yuan Luo, Julius Judd, Shayne Wierbowski, Marta Bertolotti and 12 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Yadi ZhouGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.
Yuan LiuWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.
Shagun GuptaWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.
Mauricio I ParamoWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.ORCID 0000-0002-9518-1881
Yuan HouGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.
Chengsheng MaoDivision of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University, Chicago, IL 60611, US.
Yuan LuoDivision of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University, Chicago, IL 60611, US.
Julius JuddDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, US.
Shayne WierbowskiWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.
Marta BertolottiWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.
Mriganka NerkarDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, US.
Lara JehiLerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.
Nir DraymanPritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, US.
Vlad NicolaescuDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL 60637, US.
Haley GulaDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL 60637, US.
Savaş TayPritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, US.
Glenn RandallDepartment of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL 60637, US.
John T LisDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, US.
Cédric FeschotteDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, US.
Serpil C ErzurumLerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.
Feixiong ChengGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, US.
Haiyuan YuWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, US.
Cornell University · USCleveland Clinic · USUniversity of Chicago · USNorthwestern University · US

Funding

Structure, Function, and Dynamics of Macro-molecular Complexes that Execute and Regulate Genome FunctionRM1GM139738 · NIGMS · CORNELL UNIVERSITY · PI Thomas George Wade Graham, Steven Zvi Josefowicz · 2021 to 2026
$14.4M
Endophenotype Network-based Approaches to Prediction and Population-based Validation of In Silico Drug Repurposing for Alzheimer's DiseaseR01AG066707 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng · 2020 to 2026
$4.9M
Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics DiscoveryU01AG073323 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2025
$4.0M
Integrated high-throughput functional assays to identify ulcerative colitis causal risk variantsR01DK115398 · NIDDK · CORNELL UNIVERSITY · PI KLEIN, ROBERT J., YU, HAIYUAN · 2018 to 2022
$3.3M
Interface-resolution domain-domain interactome map of the yeast complexomeR01GM130885 · NIGMS · DANA-FARBER CANCER INST · PI VIDAL, MARC · 2019 to 2022
$2.7M
Quantifying molecular consequences of human missense variants with large-scale interactome perturbation studiesR01GM125639 · NIGMS · CORNELL UNIVERSITY · PI ALEXOV, EMIL GEORGIEV, CLARK, ANDREW G · 2018 to 2021
$2.6M
Towards a comprehensive multiscale 3D human interactome networkR01GM124559 · NIGMS · CORNELL UNIVERSITY · PI YU, HAIYUAN · 2017 to 2020
$1.5M
Multimodal single-cell genomic and epigenomic analyses elucidate Alzheimer’s sexual dimorphism in human immune systems agingR56AG074001 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2021
$1.2M
NIA NIH HHS R01 AG066707NIA NIH HHS R56 AG074001NIA NIH HHS U01 AG073323NIDDK NIH HHS R01 DK115398NIGMS NIH HHS R01 GM124559NIGMS NIH HHS R01 GM125639NIGMS NIH HHS R01 GM130885NIGMS NIH HHS RM1 GM139738
6 · The paper itself

Abstract

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%,

Identifiers

PMID35677070
PMCPMC9176654
OpenAlexW4281666524

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.