MassIVE MSV000096435

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Interaction Landscape of Ancestral and Variants SCoV2-Human Protein Assemblies Revealed in Distinct Organs and Body Fluids of COVID-19 Patients

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Description

Knowledge of SARS-CoV2 (SCoV2) human protein-protein interactions (PPIs), and host response to viral infection is key to designing new antivirals to thwart COVID-19. Yet, it remains unclear how ancestral and variants SCoV2 detected in many body parts or fluids remodel virus-host protein assemblies. Here, we performed >600 affinity-purifications by tagging and expressing 28 SCoV2 proteins, and spike protein from ancestral and four variants in eight cell lines, derived from five mammalian organs or biofluid, and identified human proteins associated with each viral protein by mass spectrometry (MS). The ensuing high-quality and previously unreported SCoV2-human PPIs were largely organ or variant-specific. Besides confirming these PPIs in COVID-19 patients saliva by MS-based co-fractionation, host PPIs were altered between variants and ancestral SCoV2. We show SCoV2 NSP3 papain-like protease is a secreted protein that binds with fibrinogen to promote abnormal blood clots, and with interferon-induced proteins to evade host innate immunity. Deep-learning aided design of peptide inhibitors impeded SCoV2 and variants replication in human liver cells, and restored PPI changes by the virus to healthy state. Our results unveil new mechanisms for human-ancestral or variants SCoV2 PPIs in various organs or biofluids, offering potential host therapeutic targets and SCoV2 inhibitors for antiviral development. [doi:10.25345/C5CZ32H3Q] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: CF-MS ; Saliva ; Host-Viral PPI ; VoCs ; Spike variants ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Dr. Mohan Babu, Department of Biochemistry Room 232, Research and Innovation Centre University of Regina Regina, Saskatchewan S4S 0A2, Canada
Submitting User: srphanse
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Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

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Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

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Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.