Back

FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection

Baazim, H.; Koyuncu, E.; Tuncman, G.; Burak, M. F.; Merkel, L.; Bahour, N.; Karabulut, E.; Lee, G. Y.; Hanifehnezhad, A.; Karagoz, Z. F.; Foldes, K.; Engin, I.; Erman, A. G.; Oztop, S.; Filazi, N.; Gul, B.; Ceylan, A.; Cinar, O. O.; Can, F.; Kim, H.; Al-Hakeem, A.; Li, H.; Semerci, F.; Lin, X.; Yilmaz, E.; Ergonul, O.; Ozkul, A.; Hotamisligil, G. S.

2024-02-12 microbiology
10.1101/2024.02.10.579717 bioRxiv
Show 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-CoV2 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.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.