Kidney injury molecule-1 is a potential receptor for SARS-CoV-2

• 作者: Chen Yang Yu Zhang Xia Zeng Huijing Chen Yuchen Chen Dong Yang Ziwei Shen Xiaomu Wang Xinran Liu Mingrui Xiong Hong Chen Kun Huang
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: Articles
• 页码范围: 185-196
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab003

摘要

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 dem-onstrate 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 block-aded 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.