tetano
Editor, Senior Moderator
J Mol Cell Biol
. 2021 Jan 25;mjab003.
doi: 10.1093/jmcb/mjab003. Online ahead of print.
Kidney injury molecule-1 is a potential receptor for SARS-CoV-2
Chen Yang[SUP] 1 [/SUP], Yu Zhang[SUP] 1 [/SUP], Xia Zeng[SUP] 1 [/SUP], Huijing Chen[SUP] 1 [/SUP], Yuchen Chen[SUP] 1 [/SUP], Dong Yang[SUP] 1 [/SUP], Ziwei Shen[SUP] 1 [/SUP], Xiaomu Wang[SUP] 1 [/SUP], Xinran Liu[SUP] 1 [/SUP], Mingrui Xiong[SUP] 1 [/SUP], Hong Chen[SUP] 1 [/SUP], Kun Huang[SUP] 1 2 [/SUP]
Affiliations
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, co-immunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labelling, 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 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 receptor-binding domain 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 receptor-binding domains 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.
Keywords: COVID-19; SARS-CoV-2; coronavirus; kidney diseases; kidney injury molecule-1.
. 2021 Jan 25;mjab003.
doi: 10.1093/jmcb/mjab003. Online ahead of print.
Kidney injury molecule-1 is a potential receptor for SARS-CoV-2
Chen Yang[SUP] 1 [/SUP], Yu Zhang[SUP] 1 [/SUP], Xia Zeng[SUP] 1 [/SUP], Huijing Chen[SUP] 1 [/SUP], Yuchen Chen[SUP] 1 [/SUP], Dong Yang[SUP] 1 [/SUP], Ziwei Shen[SUP] 1 [/SUP], Xiaomu Wang[SUP] 1 [/SUP], Xinran Liu[SUP] 1 [/SUP], Mingrui Xiong[SUP] 1 [/SUP], Hong Chen[SUP] 1 [/SUP], Kun Huang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33493263
- DOI: 10.1093/jmcb/mjab003
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, co-immunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labelling, 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 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 receptor-binding domain 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 receptor-binding domains 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.
Keywords: COVID-19; SARS-CoV-2; coronavirus; kidney diseases; kidney injury molecule-1.