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Updated: Jun 16, 2026
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Engineered 3D Silk-collagen-based Model of Polarized Neural Tissue
Published on: October 23, 2015
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SARS-CoV-2 Bottlenecks and Tissue-Specific Adaptation in the Central Nervous System
Justin Richner1, Jacob Class1, Lacy Simons2
1University of Illinois at Chicago.
Research Square
|October 4, 2023
Summary
The Spike furin cleavage site (FCS) is crucial for SARS-CoV-2 neuroinvasion. Modifying the FCS impacts viral evolution and virulence in the central nervous system (CNS), offering insights into treating neuroinvasive COVID-19.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Severe COVID-19 and its sequelae can involve neurological complications, potentially due to direct central nervous system (CNS) infection by SARS-CoV-2.
- The evolutionary factors driving SARS-CoV-2 neuroinvasion remain poorly understood.
Approach:
- This study investigated SARS-CoV-2 evolution within the lung and CNS of infected mice.
- Viral diversity and mutations, particularly in the Spike furin cleavage site (FCS), were analyzed after intranasal and intracranial inoculation.
Key Points:
- Higher viral diversity and specific mutations in the FCS were observed in the CNS compared to the lung.
- Deletion of the FCS significantly reduced viral virulence and morbidity after intranasal challenge.
- Restoring the FCS via intracranial inoculation or reversion allowed the virus to regain virulence and infect the lung.
Conclusions:
- The FCS plays a critical role in SARS-CoV-2 tropism, compartmentalization, and neuroinvasion.
- Understanding FCS dynamics is essential for developing strategies to treat neuroinvasive COVID-19.
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