BREAKING! Brazilian Proteomic Study Finds That 1,652 Human Proteins Involved In Key Cellular Pathways Are Dysregulated By SARS-CoV-2!

COVID19 News: The COVID-19 pandemic, caused by the rapid spread of the SARS-CoV-2 virus, has not only challenged healthcare systems worldwide but has also sparked an unprecedented surge in scientific research aimed at understanding the intricacies of viral infection and its impact on human biology. While initially characterized as a respiratory illness, COVID-19 has since revealed its systemic nature, affecting a myriad of tissues and organs beyond the respiratory system. To delve deeper into the molecular mechanisms underlying SARS-CoV-2 infection, a groundbreaking proteomic study covered in this COVID-19 News report, conducted by researchers from the University of Campinas (UNICAMP) and the University of São Paulo (USP) in Brazil has unveiled a wealth of insights into how the virus dysregulates key cellular pathways and proteins across various human cell types.


SARS-CoV-2 infects cells from different tissues and elicits changes in protein abundance. (A) Cell lines from distinct tissues and biological systems were infected with SARS-CoV-2 in vitro and the infectomes (proteins differentially regulated due to viral response) were obtained by shotgun proteomics. (B) Total number of identified proteins (gray) and differentially regulated proteins (colored) in each cell type. (C) Proteins differentially regulated in the respective infectomes separated by direction of regulation. Bubble size indicates the number of differentially expressed proteins (DEPs). (D) Overview of SARS-CoV-2 infectome in all cell types (outer circle), showing proteins that are shared among groups as well as their respective regulation in the heatmap (inner circle). (E) Sankey plot of pathways enriched in at least 50% of infectomes.

The Pervasive Nature of SARS-CoV-2 Infection
One of the defining features of SARS-CoV-2 is its ability to infect a wide range of cell types throughout the human body. While the virus primarily gains entry into cells through the angiotensin-converting enzyme 2 (ACE2) receptor, alternative receptors such as TMPRSS2, NPR1, and BSG/CD147 have also been identified as facilitators of viral entry. Once inside the host cell, SARS-CoV-2 initiates a cascade of molecular events that lead to proteomic alterations, disrupting essential cellular processes and potentially contributing to the diverse array of symptoms observed in COVID-19 patients.
 
A Comprehensive Approach to Proteomic Analysis
To comprehensively investigate the impact of SARS-CoV-2 on human cells, the research team employed a diverse array of cell models representing different tissues and organ systems. These included neural stem cell-derived astrocytes and neurons, intestinal epithelial cells (CACO-2), immune cells such as T-cells and monocytes, hepatocytes, and adipocytes. By infecting these cells with SARS-CoV-2 in vitro, the researchers created a controlled environment to study proteomic dysregulations induced by viral infection across var ious cell types.
 
Insights from Proteomic Data
The proteomic analyses yielded a wealth of data, with 3098 proteins quantified and 1652 showing significant dysregulation in response to SARS-CoV-2 infection. Notably, the study highlighted the reproducibility of data, minimal missing values, and the identification of key proteins involved in fundamental cellular pathways. These dysregulated proteins encompassed a wide range of cellular functions, including those related to cellular structure, energy metabolism, immune response, and inflammatory signaling.
 
Cellular Heterogeneity and Pathway Dysregulation
One of the striking findings of the study was the heterogeneity of protein dysregulation across different cell types. While certain pathways such as energy metabolism and immune response were commonly affected, each cell type also exhibited unique dysregulated proteins and pathways. For example, neuronal cell models showed a distinct pattern of upregulated proteins in their infectomes, whereas immune cells displayed alterations in pathways related to phagocytosis and cytokine signaling. This heterogeneity underscores the complex interplay between viral infection and cell-specific responses.
 
The Emergence of the SARS-CoV-2 Infectome Atlas
Central to the study's findings is the creation of the SARS-CoV-2 Infectome Atlas, a comprehensive database cataloging proteomic dysregulations induced by SARS-CoV-2 across nine distinct cellular infectomes. This atlas serves as a valuable resource for researchers, providing detailed information on dysregulated proteins, altered pathways, and tissue-specific responses to viral infection. The interactive online platform facilitates the exploration of dysregulated proteins and pathways, fostering a collaborative environment for ongoing investigations into COVID-19 biology and treatment strategies.
 
Diving into Specific Tissue Responses
The study delved into tissue-specific responses to SARS-CoV-2 infection, shedding light on how the virus modulates proteomes in different organ systems. For instance, in the central nervous system (CNS), neuronal infectomes exhibited a higher degree of dysregulation compared to astrocytes, implicating potential vulnerabilities of specific cell types to viral infection. Similarly, gastroenterological cells displayed alterations in pathways related to inflammation, energy metabolism, and cellular homeostasis, reflecting the diverse clinical manifestations observed in COVID-19 patients.

Implications for COVID-19 Pathogenesis and Therapeutics
The insights gleaned from this proteomic study have significant implications for understanding COVID-19 pathogenesis and developing targeted therapeutics. Dysregulation of energy metabolism pathways emerged as a common theme across different cell types, suggesting a potential vulnerability of infected cells that could be exploited for therapeutic interventions. Furthermore, the identification of tissue-specific proteomic signatures offers valuable clues for designing tailored treatment strategies that address the diverse clinical manifestations of COVID-19.
 
Future Directions and Collaborative Research
Moving forward, the collaborative and data-driven nature of this research paves the way for future investigations into SARS-CoV-2 pathogenesis and treatment. The integration of proteomic data into the SARS-CoV-2 Infectome Atlas provides a framework for ongoing research initiatives, enabling researchers worldwide to contribute and access critical information related to viral infection and cellular responses. Collaborative efforts aimed at deciphering the intricacies of SARS-CoV-2 proteomic dysregulations are essential for advancing our understanding of COVID-19 and developing effective therapeutic interventions.
 
Conclusion
In conclusion, the Brazilian proteomic study on SARS-CoV-2 infection represents a significant milestone in unraveling the molecular complexities of COVID-19. By elucidating key dysregulated proteins and pathways across diverse human cell types, this research not only enhances our understanding of viral pathogenesis but also provides a roadmap for targeted therapeutic strategies. As the global scientific community continues to confront the challenges posed by the COVID-19 pandemic, collaborative research endeavors such as this proteomic study serve as beacons of hope in the quest for effective treatments and mitigating the impact of viral infections on human health.
 
The study findings and the access to the SARS-CoV-2 Infectome Atlas were published in the peer reviewed journal: Scientific Reports (Nature).
https://www.nature.com/articles/s41598-024-56328-3
 
Thailand Medical News would like to add that based on our own collation of data from various studies and research over the past 4 years, there are actually over 2,874 (This number keeps on increasing as new studies emerge) different cellular pathways, genes, key proteases that are either upregulated, downregulated, dysregulated or damaged by the SARS-CoV-2 virus but we have just only started compiling all the data on the thousands of viral peptides that are not part of the virus RNA genomic structure but which are produced during replication and was once thought to be simply junk proteins but have now come to be found to be pathogenic as they can bind to various human proteases as well and cause effects!
 
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