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FABP4 as a therapeutic host target controlling SARS-CoV-2 infection
Hatoon Baazim1, Emre Koyuncu2, Gürol Tuncman1
1Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
EMBO Molecular Medicine
|January 22, 2025
Summary
Fatty acid-binding protein 4 (FABP4) drives severe COVID-19 by promoting SARS-CoV-2 replication. Inhibiting FABP4 reduces viral load and lung damage, offering a potential therapeutic strategy.
Area of Science:
- Infectious disease
- Host-pathogen interactions
- Metabolic disorders
Background:
- Host metabolic health significantly impacts infectious disease severity.
- Obesity and aging are risk factors for severe respiratory infections, including COVID-19, but mechanisms are unclear.
- Fatty acid-binding protein 4 (FABP4) links metabolic dysfunction and inflammation.
Purpose of the Study:
- To investigate the role of FABP4 in SARS-CoV-2 pathogenesis.
- To explore FABP4 as a potential therapeutic target for COVID-19.
Main Methods:
- Assessed FABP4 expression and correlation with COVID-19 severity.
- Utilized genetic and pharmacological inhibition of FABP4 in cell culture models (adipocytes, airway epithelial cells).
- Evaluated FABP4 inhibitor efficacy in a hamster model of SARS-CoV-2 infection.
Main Results:
- FABP4 expression strongly correlated with COVID-19 disease severity.
- Loss of FABP4 function reduced SARS-CoV-2 replication and viral organelle formation.
- FABP4 inhibition in hamsters decreased lung viral titers, lung damage, and collagen deposition.
Conclusions:
- FABP4 is a key host factor modulating SARS-CoV-2 pathogenesis.
- Targeting FABP4 represents a promising therapeutic strategy to combat coronavirus infections.
- Host metabolic pathways are critical targets for controlling viral replication and disease progression.
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