Journal
JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 13, Issue 3, Pages 185-196Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjab003
Keywords
SARS-CoV-2; COVID-19; kidney diseases; kidney injury molecule-1; coronavirus
Categories
Funding
- Natural Science Foundation of China [31971066, 31871411, 31671195]
- Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College
- HUST [2020yjsCXCY042]
- HUST
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Research has identified KIM1 as a novel receptor for SARS-CoV-2, potentially exacerbating renal infection; KIM1 could be further explored as a therapeutic target.
COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, coimmunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labeling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain (RBD) of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a 'vicious cycle', and KIM1 could be further explored as a therapeutic target.
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