RESEARCH ARTICLE


ACE2 Shedding and Furin Abundance in Target Organs may Influence the Efficiency of SARS-CoV-2 Entry



Yuanchen Ma1, #, Yinong Huang1, 2, #, Tao Wang1, Andy Peng Xiang1, Weijun Huang1, *
1 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
2 Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Er Road, Guangzhou, Guangdong 510080, China.


© 2021 Ma et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong 510080, China; E-mail: hweijun@mail.sysu.edu.cn# Contributed equally to this work.


Abstract

Background:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a lineage B coronavirus, causing the 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.

Methods:

To solve this problem, we use the online single-cell sequence datasets to analyze the expression of the major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases.

Results:

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 an 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.

Conclusion:

Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

Keywords: SARS-CoV-2, scRNA-seq, ACE2, Endopeptidase, Furin, Viral entry.