medRxiv. 2020 Sep 18; doi: 10.1101/2020.09.16.20190694.

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

medRxiv : the preprint server for health sciences

Takaharu Ichimura, Yutaro Mori, Philipp Aschauer, Krishna M Padmanabha Das, Robert F Padera, Astrid Weins, Mahmoud L Nasr, Joseph V Bonventre

PMID: 32995803 PMCID: PMC7523142 DOI: 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.

Publication Types

• Preprint

Grant support

• R01 DK072381/DK/NIDDK NIH HHS/United States
• R37 DK039773/DK/NIDDK NIH HHS/United States
• UH3 TR002155/TR/NCATS NIH HHS/United States