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Effect of β-chitosan on the binding interaction between SARS-CoV-2 S-RBD and ACE2
bioRxiv - Biochemistry Pub Date : 2020-09-18 , DOI: 10.1101/2020.07.31.229781
Gulimiran Alitongbieke , Xiu-Min Li , Qi-Ci Wu , Zhi-Chao Lin , Jia-Fu Huang , Yu Xue , Jing-Na Liu , Jin-Mei Lin , Tao Pan , Yi-Xuan Chen , Yi Su , Guo-Guang Zhang , Bo Leng , Shu-Wen Liu , Yu-Tian Pan

SARS-CoV-2 invades human respiratory epithelial cells via an interaction between its spike RBD protein (SARS-CoV-2 S-RBD) and the host cell receptor angiotensin converting enzyme II (ACE2). Blocking this interaction provides a potent approach to preventing and controlling SARS-CoV-2 infection. In this work, the ability of β-chitosan to block the binding interaction between SARS-CoV-2 S-RBD and ACE2 was investigated. The inhibitory effect of β-chitosan on inflammation induced by the SARS-CoV-2 S-RBD was also studied. Native-PAGE analysis indicated that β-chitosan could bind with ACE2 and the SARS-CoV-2 S-RBD and a conjugate of β-chitosan and ACE2 could no longer bind with the SARS-CoV-2 S-RBD. HPLC analysis suggested that a conjugate of β-chitosan and the SARS-CoV-2 S-RBD displayed high binding affinity without dissociation under high pressure (40 MPa) compared with that of β-chitosan and ACE2. Furthermore, immunofluorescent staining of Vero E6 cells and lungs from hACE2 mice showed that the presence of β-chitosan prevented SARS-CoV-2 S-RBD from binding to ACE2. Meanwhile, β-chitosan could dramatically suppress the inflammation caused by the presence of the SARS-CoV-2 S-RBD both in vitro and vivo. Moreover, the decreased expression of ACE2 caused by β-chitosan treatment was restored by addition of TAPI-1, an inhibitor of the transmembrane protease ADAM17. Our findings demonstrated that β-chitosan displays an antibody-like function capable of neutralizing the SARS-CoV-2 S-RBD and effectively preventing the binding of the SARS-CoV-2 S-RBD to ACE2. Moreover, ADAM17 activation induced by β-chitosan treatment can enhance the cleavage of the extracellular domain of ACE2, releasing the active ectodomain into the extracellular environment, which can prevent the binding, internalization, and degradation of ACE2 bound to the SARS-CoV-2 S-RBD and thus diminish inflammation. Our study provides an alternative avenue for preventing SARS-CoV-2 infection using β-chitosan.

中文翻译:

β-壳聚糖对SARS-CoV-2 S-RBD与ACE2结合相互作用的影响

SARS-CoV-2通过其尖峰RBD蛋白(SARS-CoV-2 S-RBD)与宿主细胞受体血管紧张素转化酶II(ACE2)之间的相互作用侵入人呼吸道上皮细胞。阻止这种相互作用提供了一种有效的方法来预防和控制SARS-CoV-2感染。在这项工作中,研究了β-壳聚糖阻断SARS-CoV-2 S-RBD与ACE2之间的结合相互作用的能力。还研究了β-壳聚糖对SARS-CoV-2 S-RBD诱导的炎症的抑制作用。天然PAGE分析表明,β-壳聚糖可以与ACE2和SARS-CoV-2 S-RBD结合,而β-壳聚糖和ACE2的结合物不再与SARS-CoV-2S-RBD结合。HPLC分析表明,与β-壳聚糖和ACE2相比,β-壳聚糖和SARS-CoV-2 S-RBD的结合物在高压(40 MPa)下显示出高结合亲和力而不会解离。此外,来自hACE2小鼠的Vero E6细胞和肺部的免疫荧光染色显示,β-壳聚糖的存在阻止SARS-CoV-2 S-RBD与ACE2结合。同时,β-壳聚糖可以显着抑制由SARS-CoV-2 S-RBD的存在引起的炎症体外体内。此外,通过添加跨膜蛋白酶ADAM17的抑制剂TAPI-1,恢复了由β-壳聚糖处理引起的ACE2表达降低。我们的发现表明,β-壳聚糖显示出能够中和SARS-CoV-2 S-RBD并有效防止SARS-CoV-2 S-RBD与ACE2结合的抗体样功能。此外,β-壳聚糖处理诱导的ADAM17激活可以增强ACE2胞外域的切割,将活性胞外域释放到胞外环境中,从而可以阻止与SARS-CoV-2结合的ACE2的结合,内化和降解。 S-RBD,从而减轻炎症。我们的研究为使用β-壳聚糖预防SARS-CoV-2感染提供了另一种途径。
更新日期:2020-09-20
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