Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of 2019-nCov entry

Mei, Z.; Bingpeng, L.; Hongbin, G.; Xinhong, W.; Kaibin, W.; Mingxiao, L.; Chang, L.; Jianming, C.; Learn-han, L.; Cuiling, Q.; Linhu, G.; Lijing, W.

doi:10.1101/2020.04.18.047951

bioRxiv · 10.1101/2020.04.18.047951

Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of 2019-nCov entry

Mei, Z.·Bingpeng, L.·Hongbin, G.·Xinhong, W.·Kaibin, W.·Mingxiao, L.·Chang, L.·Jianming, C.·Learn-han, L.·Cuiling, Q.·Linhu, G.·Lijing, W.

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Abstract

Background Leading to a sustained epidemic spread with >40,000 confirmed human infections, including >10,000 deaths, COVID-19 was caused by 2019-nCov 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 2019-nCov 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 2019-nCov. Moreover, it has been reported that ACE2 is likely to be the receptor for 2019-nCoV. 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 2019-nCov 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 2019-nCov, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Mei, Z., Bingpeng, L., Hongbin, G., Xinhong, W., Kaibin, W., Mingxiao, L., Chang, L., Jianming, C., Learn-han, L., Cuiling, Q., Linhu, G., Lijing, W.. 2020-04-18. Significant expression of FURIN and ACE2 on oral epithelial cells may facilitate the efficiency of 2019-nCov entry. https://doi.org/10.1101/2020.04.18.047951

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