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 SAR...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.展开更多
基金supported by the Natural Science Foundation of China(31971066,31871A11,and 31671195)the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical Collegethe Front Youth Program of HUST,and Innovation Funding Project of HUST(2020yjsCXCY042).
文摘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.
