KIM 1/TIM 1 is a Receptor for SARS CoV 2 in Lung and Kidney
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.
medRxiv