Dataset Information

Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.

ABSTRACT:

Aim

The present study aimed to identify human protein-host protein interactions of SARS-CoV-2 infection in the small intestine to discern the potential mechanisms and gain insights into the associated biomarkers and treatment strategies.

Background

Deciphering the tissue and organ interactions of the SARS-CoV-2 infection can be important to discern the potential underlying mechanisms. In the present study, we investigated the human protein-host protein interactions in the small intestine.

Methods

Public databases and published works were used to collect data related to small intestine tissue and SARS-CoV-2 infection. We constructed a human protein-protein interaction (PPI) network and showed interactions of host proteins in the small intestine. Associated modules, biological processes, functional pathways, regulatory transcription factors, disease ontology categories, and possible drug candidates for therapeutic targets were identified.

Results

Thirteen primary protein neighbors were found for the SARS-CoV-2 receptor ACE2. ACE2 and its four partners were observed in a highly clustered module; moreover, 8 host proteins belonged to this module. The protein digestion and absorption as a significant pathway was highlighted with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2. The HNF4A, HNF1A, and HNF1B transcription factors were found to be regulating the expression of ACE2. A significant association with 12 diseases was deciphered and 116 drug-target interactions were identified.

Conclusion

The protein-host protein interactome revealed the important elements and interactions for SARS-CoV-2 infection in the small intestine, which can be useful in clarifying the mechanisms of gastrointestinal symptoms and inflammation. The results suggest that antiviral targeting of these interactions may improve the condition of COVID-19 patients.

SUBMITTER: Khodadoost M

PROVIDER: S-EPMC7682973 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.

Khodadoost Mahmoud M Niknam Zahra Z Farahani Masoumeh M Razzaghi Mohammadreza M Norouzinia Mohsen M

Gastroenterology and hepatology from bed to bench 20200101 4

<h4>Aim</h4>The present study aimed to identify human protein-host protein interactions of SARS-CoV-2 infection in the small intestine to discern the potential mechanisms and gain insights into the associated biomarkers and treatment strategies.<h4>Background</h4>Deciphering the tissue and organ interactions of the SARS-CoV-2 infection can be important to discern the potential underlying mechanisms. In the present study, we investigated the human protein-host protein interactions in the small in ...[more]

PMID: 33244381

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Project 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.

Dataset Information

Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.

Aim

Background

Methods

Results

Conclusion

Publications

Investigating the human protein-host protein interactome of SARS-CoV-2 infection in the small intestine.

Similar Datasets

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