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.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, Kidney diseases, kidney injury molecule-1, 【초록키워드】 Mortality, SARS-CoV, Infection, in silico, MERS-CoV, respiratory diseases, Kidney injury, kidney, pathogen, Immunoglobulin, RBD, peptides, receptor, incidence, Interaction, COVID-19 patient, therapeutic target, SARS-CoV-2 RBD, energy transfer, other coronaviruses, domain, poor prognosis, Abnormalities, renal, cell membrane, labeling, bind, addition, facilitate, the RBD, the receptor-binding domain, upregulated, exacerbate, fluorescein isothiocyanate, tropism of SARS-CoV-2, 【제목키워드】 receptor, Injury,