ACE2 shedding and furin abundance in target organs may influence the efficiency of SARS-CoV-2 entry

分类： 医学、药学 >> 基础医学 提交时间： 2020-02-27

Yuanchen Ma Yinong Huang Tao Wang Andy Peng Xiang Weijun Huang

摘要： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified lineage B coronavirus, causing rapid worldwide outbreak of Corona Virus Disease 2019 (COVID-19). Despite genetically closed to SARS-CoV, SARS-CoV-2 seems to possess enhanced infectivity and subtle different clinical features, which may hamper the early screening of suspected patients as well as the control of virus transmission. Unfortunately, there are few tools to predict the potential target organ damage and possible clinical manifestations caused by such novel coronavirus. To solve this problem, we investigate the potential host cell entry mechanisms of SARS-CoV-2 through bioinformatics. Using the online single-cell sequence datasets, we analyze the expression of major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases. The results indicated the differential expression of ADAM10 and ADAM17 might contribute to the ACE2 shedding and affect the membrane ACE2 abundance. We further confirm a putative furin-cleavage site reported recently in the spike protein of SARS-CoV-2, which may facilitate the virus-cell fusion. Based on these findings, we develop a novel approach that comprehensively analyzed the virus receptor expression, ACE2 shedding, membrane fusion activity, virus uptake and virus replication to evaluate the infectivity of SARS-CoV-2 to different human organs. Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

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