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bioRxiv · 10.1101/2020.10.09.334052

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

Yang, C.·Zhang, Y.·Chen, H.·Chen, Y.·Yang, D.·Shen, Z.·Wang, X.·Liu, X.·Xiong, M.·Huang, K.
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Abstract

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and high mortality. Identification of SARS-CoV-2 in kidney of COVID-19 patients suggests renal tropism and direct infection. Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Kidney injury molecule-1 (KIM1) is a transmembrane protein that drastically up-regulated after renal injury. Here, binding between SARS-CoV2-RBD and the extracellular Ig V domain of KIM1 was identified by molecular simulations and co-immunoprecipitation, which was comparable in affinity to that of ACE2 to SARS-CoV-2. Moreover, KIM1 facilitated cell entry of SARS-CoV2-RBD, which was potently blockaded by a rationally designed KIM1-derived polypeptide. Together, the findings suggest KIM1 may mediate and exacerbate SARS-CoV-2 infection in a vicious cycle, and KIM1 could be further explored as a therapeutic target.

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Yang, C., Zhang, Y., Chen, H., Chen, Y., Yang, D., Shen, Z., Wang, X., Liu, X., Xiong, M., Huang, K.. 2020-10-10. Kidney injury molecule-1 is a potential receptor for SARS-CoV-2. https://doi.org/10.1101/2020.10.09.334052

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