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KIM-1/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney (preprint)
medrxiv; 2020.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2020.09.16.20190694
ABSTRACT
SARS-CoV-2 precipitates respiratory distress by infection of airway epithelial cells and is often accompanied by acute kidney injury. We report that Kidney Injury Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) is expressed in lung and kidney epithelial cells in COVID-19 patients and is a receptor for SARS-CoV-2. Human and mouse lung and kidney epithelial cells express KIM-1 and endocytose nanoparticles displaying the SARS-CoV-2 spike protein (virosomes). Uptake was inhibited both by anti-KIM-1 antibodies and by TW-37, our newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 positive cells express less angiotensin-converting enzyme 2 (ACE2), the well-known receptor for SARS-CoV-2. Using microscale thermophoresis, the EC50 for KIM-1-SARS-CoV-2 spike protein, and receptor binding domain (RBD) interactions, were 19 and 10 nM respectively. Thus KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Acute Kidney Injury
/
COVID-19
/
Kidney Diseases
Language:
English
Year:
2020
Document Type:
Preprint
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