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Kidney injury molecule-1 is a potential receptor for SARS-CoV-2
Chen Yang1,† , Yu Zhang1,† , Xia Zeng1 , Huijing Chen1 , Dong Yang1 , Yuchen Chen1 , Ziwei Shen1 , Xiaomu Wang1 , Xinran Liu1 , Mingrui Xiong1 , Hong Chen1,* , Kun Huang1,2,*
1School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2Tongji-RongCheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
These authors contributed equally to this work.
*Correspondence to:Hong Chen , Kun Huang ,
J Mol Cell Biol, Volume 13, Issue 3, March 2021, 185-196,
Keyword: SARS-CoV-2, COVID-19, kidney diseases, kidney injury molecule-1, coronavirus

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.