PT  - JOURNAL ARTICLE
AU  - Gulimiran Alitongbieke
AU  - Xiu-min Li
AU  - Qi-Ci Wu
AU  - Zhi-Chao Lin
AU  - Jia-Fu Huang
AU  - Yu Xue
AU  - Jing-Na Liu
AU  - Jin-Mei Lin
AU  - Tao Pan
AU  - Yi-Xuan Chen
AU  - Yi Su
AU  - Guo-Guang Zhang
AU  - Bo Leng
AU  - Shu-Wen Liu
AU  - Yu-Tian Pan
TI  - Study on β-Chitosan against the binding of SARS-CoV-2S-RBD/ACE2
AID  - 10.1101/2020.07.31.229781
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.31.229781
4099  - http://biorxiv.org/content/early/2020/07/31/2020.07.31.229781.short
4100  - http://biorxiv.org/content/early/2020/07/31/2020.07.31.229781.full
AB  - It has been known that SARS-CoV-2 which is considered similar to SARS-CoV invades human respiratory epithelial cells through interaction with the human angiotensin converting enzyme II (ACE2). In this work, SARS-CoV-2S-RBD and its cell receptor ACE2 were used to investigate the blocking effect and mechanism of β-chitosan to the binding of them. Besides, inhibitory effect of β-chitosan on inflammation induced by SARS-CoV-2S-RBD was also studied. Firstly, Native-PAGE results showed that β-chitosan could bind with ACE2 or SARS-CoV-2S-RBD and the conjugate of β-chitosan and ACE2 could no longer bind with SARS-CoV-2S-RBD. HPLC analyses suggested that was found the conjugate of β-chitosan and SARS-CoV-2S-RBD displayed high binding affinity under the condition of high pressure (40 MPa) compared with that of ACE2 and SARS-CoV-2S-RBD. Furthermore, immunofluorescence detections on Vero E6 cells and hACE2 mice showed that β-chitosan had a significant prevention and treatment effect on SARS-CoV-2S-RBD binding. Meanwhile, SARS-CoV-2S-RBD binding could activate the inflammation signaling pathways of cells and mice, however, β-chitosan could dramatically suppress the inflammations activated by SARS-CoV-2S-RBD. Subsequently, Western blot analyses revealed that the expression levels of ACE2 in experimental groups treated with β-chitosan significantly reduced. However, after the intervention of ADAM17 inhibitor (TAPI), the decreased ACE2 expressions affected by β-chitosan up-regulated correspondingly. The results indicated that β-chitosan has a similar antibody function, which can neutralize SARS-CoV-2S-RBD and effectively block the binding of SARS-CoV-2S-RBD with ACE2. ADAM17 activated by β-chitosan can enhance the cleavage of ACE2 extracellular domain with a catalytic activity of Ang II degradation, and then the extracellular region was released into the extracellular environment. So, β-chitosan could prevent the binding, internalization and degradation of ACE2 with SARS-CoV-2S-RBD and inhibit the activation of inflammatory signaling pathways at the same time. This work provides a valuable reference for the prevention and control of SARS-CoV-2 by β-chitosan.Competing Interest StatementThe authors have declared no competing interest.