Kidney injury molecule-1 is a potential receptor for SARS-CoV-2. (25th January 2021)

• Record Type: Journal Article
• Authors: Yang, Chen; Zhang, Yu; Zeng, Xia; Chen, Huijing; Chen, Yuchen; Yang, Dong; Shen, Ziwei; Wang, Xiaomu; Liu, Xinran; Xiong, Mingrui; Chen, Hong; Huang, Kun
• Editors: Fu, Haian
• Is Part Of: Journal of molecular cell biology. Volume 13:Number 3(2021)
• Page Start: 185
• Page End: 196
• Publication Date: 2021-01-25
• Subjects: SARS-CoV-2 -- COVID-19 -- kidney diseases -- kidney injury molecule-1 -- coronavirus; Molecular biology -- Periodicals; 571.605
• DOI: 10.1093/jmcb/mjab003
• Languages: English
• ISSNs: 1674-2788

Abstract

Abstract: 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.