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

Yutaro Mori; Corby Fink; Takaharu Ichimura; Keisuke Sako; Makiko Mori; Nathan N Lee; Philipp Aschauer; Krishna M Padmanabha Das; SoonGweon Hong; Minsun Song; Robert F Padera Jr.; Astrid Weins; Luke P Lee; Mahmoud L Nasr; Gregory A Dekaban; Jimmy D Dikeakos; Joseph V Bonventre

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

Yutaro Mori; Corby Fink; Takaharu Ichimura; Keisuke Sako; Makiko Mori; Nathan N Lee; Philipp Aschauer; Krishna M Padmanabha Das; SoonGweon Hong; Minsun Song; Robert F Padera Jr.; Astrid Weins; Luke P Lee; Mahmoud L Nasr; Gregory A Dekaban; Jimmy D Dikeakos; Joseph V Bonventre.

Affiliation

Yutaro Mori; Brigham and Women's Hospital, Harvard Medical School
Corby Fink; Western University
Takaharu Ichimura; Brigham and Women's Hospital, Harvard Medical School
Keisuke Sako; Brigham and Women's Hospital, Harvard Medical School
Makiko Mori; Brigham and Women's Hospital, Harvard Medical School
Nathan N Lee; Brigham and Women's Hospital, Harvard Medical School
Philipp Aschauer; Harvard Medical School
Krishna M Padmanabha Das; Harvard Medical School
SoonGweon Hong; Brigham and Women's Hospital, Harvard Medical School
Minsun Song; Brigham and Women's Hospital, Harvard Medical School
Robert F Padera Jr.; Brigham and Women's Hospital, Harvard Medical School
Astrid Weins; Brigham and Women's Hospital, Harvard Medical School
Luke P Lee; Brigham and Women's Hospital, Harvard Medical School
Mahmoud L Nasr; Brigham and Women's Hospital, Harvard Medical School
Gregory A Dekaban; Western University
Jimmy D Dikeakos; Western University
Joseph V Bonventre; Brigham and Women's Hospital, Harvard Medical School

Preprint in English | medRxiv | ID: ppmedrxiv-20190694

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ABSTRACT

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 by anti-KIM-1 antibodies and TW-37, a newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 binds to the SARS-CoV-2 Spike protein in vitro. KIM-1 expressing cells, not expressing angiotensin-converting enzyme 2 (ACE2), are permissive to SARS-CoV-2 infection. Thus, KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.

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Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2020 Document type: Preprint

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Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2020 Document type: Preprint