KIM-1/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney.
Takaharu IchimuraYutaro MoriPhilipp AschauerKrishna M Padmanabha DasRobert F PaderaAstrid WeinsMahmoud L NasrJoseph V BonventrePublished in: medRxiv : the preprint server for health sciences (2020)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- angiotensin converting enzyme
- binding protein
- acute kidney injury
- angiotensin ii
- endothelial cells
- poor prognosis
- small molecule
- induced apoptosis
- cardiac surgery
- oxidative stress
- protein protein
- transcription factor
- cell death
- respiratory tract
- endoplasmic reticulum stress
- dna binding