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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
Tau protein aggregation associated with SARS-CoV-2 main protease
Raphael Josef Eberle1,2, Mônika Aparecida Coronado1, Ian Gering1
1Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Jülich, Germany.
Abstract:
The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes. The present study describes the possible induction of tau aggregation by the SARS-CoV-2 3CL protease (3CLpro) possibly relevant in neuropathology. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.
Insights
The SARS-CoV-2 3CL protease may induce tau aggregation, a process implicated in neurodegeneration. This viral protease cleaves tau, potentially contributing to neuropathology following COVID-19 infection.
Area of Science:
- Virology
- Neuroscience
- Biochemistry
Background:
- Virus proteases cleave viral polyproteins and host proteins, impacting viral pathogenicity and cellular functions.
- COVID-19 infection is known to affect multiple organs, including the brain, with potential links to neurodegenerative processes.
Purpose of the Study:
- To investigate the potential role of SARS-CoV-2 3CL protease in inducing tau aggregation.
- To explore the implications of this interaction in COVID-19-associated neuropathology.
Main Methods:
- The study focused on the enzymatic activity of the SARS-CoV-2 3CL protease.
- Investigated the cleavage of tau protein by the viral protease.
Main Results:
- SARS-CoV-2 3CL protease was shown to proteolytically cleave tau protein.
- This cleavage resulted in the generation of tau aggregates.
Conclusions:
- The SARS-CoV-2 3CL protease may induce tau aggregation, a key feature of neurodegenerative diseases.
- Further research is required to confirm if COVID-19 infection triggers neurodegenerative diseases through this mechanism.
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