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

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.