EMBO Molecular Medicine (Jan 2025)
FABP4 as a therapeutic host target controlling SARS-CoV-2 infection
- Hatoon Baazim,
- Emre Koyuncu,
- Gürol Tuncman,
- M Furkan Burak,
- Lea Merkel,
- Nadine Bahour,
- Ezgi Simay Karabulut,
- Grace Yankun Lee,
- Alireza Hanifehnezhad,
- Zehra Firat Karagoz,
- Katalin Földes,
- Ilayda Engin,
- Ayse Gokce Erman,
- Sidika Oztop,
- Nazlican Filazi,
- Buket Gul,
- Ahmet Ceylan,
- Ozge Ozgenc Cinar,
- Fusun Can,
- Hahn Kim,
- Ali Al-Hakeem,
- Hui Li,
- Fatih Semerci,
- Xihong Lin,
- Erkan Yilmaz,
- Onder Ergonul,
- Aykut Ozkul,
- Gökhan S Hotamisligil
Affiliations
- Hatoon Baazim
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Emre Koyuncu
- Crescenta Biosciences Inc
- Gürol Tuncman
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- M Furkan Burak
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Lea Merkel
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Nadine Bahour
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Ezgi Simay Karabulut
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Grace Yankun Lee
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- Alireza Hanifehnezhad
- Ankara University, Faculty of Veterinary Medicine, Department of Virology
- Zehra Firat Karagoz
- Ankara University, Biotechnology Institute
- Katalin Földes
- The Pirbright Institute
- Ilayda Engin
- Ankara University, Biotechnology Institute
- Ayse Gokce Erman
- Ankara University, Biotechnology Institute
- Sidika Oztop
- Ankara Medipol University, School of Medicine, Department of Medical Biology
- Nazlican Filazi
- Mustafa Kemal University, Faculty of Veterinary Medicine, Department of Virology
- Buket Gul
- Ankara University, Faculty of Veterinary Medicine, Department of Virology
- Ahmet Ceylan
- Ankara University, Faculty of Veterinary Medicine, Department of Histology and Embryology
- Ozge Ozgenc Cinar
- Ankara University, Faculty of Veterinary Medicine, Department of Histology and Embryology
- Fusun Can
- Koç University, School of Medicine, Department of Infectious Diseases
- Hahn Kim
- Crescenta Biosciences Inc
- Ali Al-Hakeem
- Crescenta Biosciences Inc
- Hui Li
- Department of Biostatistics, Harvard T.H. Chan School of Public Health
- Fatih Semerci
- Crescenta Biosciences Inc
- Xihong Lin
- Department of Biostatistics, Harvard T.H. Chan School of Public Health
- Erkan Yilmaz
- Ankara University, Biotechnology Institute
- Onder Ergonul
- Koç University, School of Medicine, Department of Infectious Diseases
- Aykut Ozkul
- Ankara University, Faculty of Veterinary Medicine, Department of Virology
- Gökhan S Hotamisligil
- Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health
- DOI
- https://doi.org/10.1038/s44321-024-00188-x
- Journal volume & issue
-
Vol. 17,
no. 3
pp. 414 – 440
Abstract
Abstract Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients. We demonstrate that loss of FABP4 function, by genetic or pharmacological means, reduces SARS-CoV-2 replication and disrupts the formation of viral replication organelles in adipocytes and airway epithelial cells. Importantly, FABP4 inhibitor treatment of infected hamsters diminished lung viral titers, alleviated lung damage and reduced collagen deposition. These findings highlight the therapeutic potential of targeting host metabolism in limiting coronavirus replication and mitigating the pathogenesis of infection.
Keywords
