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Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry

Mei Zhong, Bing-peng Lin, Hong-bin Gao, Andrew J Young, Xin-hong Wang, Chang Liu, Kai-bin Wu, Ming-xiao Liu, Jian-ming Chen, Jiang-yong Huang, Learn-han Lee, Cui-ling Qi, Lin-hu Ge, Li-jing Wang
doi: https://doi.org/10.1101/2020.04.18.047951
Mei Zhong
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Bing-peng Lin
1Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Hong-bin Gao
3Guangdong Laboratory Animals Monitoring Institute, Key Laboratory of Guangdong Laboratory Animals, Guangzhou 510663, China
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Andrew J Young
4Columbus Inpatient Care, Grove City, OH 43123, USA
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Xin-hong Wang
1Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Chang Liu
5Stomatology school of Ji’nan University, Guangzhou 510000, China
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Kai-bin Wu
1Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Ming-xiao Liu
1Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Jian-ming Chen
1Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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Jiang-yong Huang
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Learn-han Lee
6Novel Bacteria and Drug Discovery Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
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Cui-ling Qi
7Vascular Biology Research Institute, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China
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Lin-hu Ge
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
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  • For correspondence: gelinhu@yeah.net wanglijing@gdpu.edu.cn
Li-jing Wang
2State Key Laboratory of Basic and Applied Research in Oral Regenerative Medicine, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, China
7Vascular Biology Research Institute, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China
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  • For correspondence: gelinhu@yeah.net wanglijing@gdpu.edu.cn
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Abstract

Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited.

Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level.

Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results.

Conclusions Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • 1.Section on discussion updated to clarify the innovation 2.Section on methods updated 3.author affiliations updated

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted April 22, 2020.
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Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry
Mei Zhong, Bing-peng Lin, Hong-bin Gao, Andrew J Young, Xin-hong Wang, Chang Liu, Kai-bin Wu, Ming-xiao Liu, Jian-ming Chen, Jiang-yong Huang, Learn-han Lee, Cui-ling Qi, Lin-hu Ge, Li-jing Wang
bioRxiv 2020.04.18.047951; doi: https://doi.org/10.1101/2020.04.18.047951
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Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of SARS-CoV-2 entry
Mei Zhong, Bing-peng Lin, Hong-bin Gao, Andrew J Young, Xin-hong Wang, Chang Liu, Kai-bin Wu, Ming-xiao Liu, Jian-ming Chen, Jiang-yong Huang, Learn-han Lee, Cui-ling Qi, Lin-hu Ge, Li-jing Wang
bioRxiv 2020.04.18.047951; doi: https://doi.org/10.1101/2020.04.18.047951

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