Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Song J, Chow RD, Pena-Hernandez M, Zhang L, Loeb SA, So E-Y, Liang OD, Wilen CB, Lee S

SARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor for SARS-CoV-2 entry. LRRC15 directly binds to the ...

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receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not co-expressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory receptor for SARS-CoV-2 regulating viral entry in trans.

Date: Nov. 24, 2021

Status: Preliminary Report

View Source: doi: 10.1101/2021.11.23.469714

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