Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A tiny viral protein, SARS-CoV-2-ORF7b: Functional molecular mechanisms.

Version 1 : Received: 26 February 2024 / Approved: 7 March 2024 / Online: 8 March 2024 (09:02:28 CET)

How to cite: Mansueto, G.; Fusco, G.; Colonna, G. A tiny viral protein, SARS-CoV-2-ORF7b: Functional molecular mechanisms.. Preprints 2024, 2024030473. https://doi.org/10.20944/preprints202403.0473.v1 Mansueto, G.; Fusco, G.; Colonna, G. A tiny viral protein, SARS-CoV-2-ORF7b: Functional molecular mechanisms.. Preprints 2024, 2024030473. https://doi.org/10.20944/preprints202403.0473.v1

Abstract

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Keywords

SARS-CoV-2-ORF7b, COVID-19, Interactomics, Topological analysis, Cluster analysis, Co-regulation network, Transcription Factors, microRNA, SARS-CoV-2 inter-tissue diffusion, programmed death.

Subject

Biology and Life Sciences, Virology

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