Effect of β-chitosan on the binding interaction between SARS-CoV-2 S-RBD and ACE2

Abstract

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.

Novel Insights Into the Sulfated Glucuronic Acid-Based Anti-SARS-CoV-2 Mechanism of Exopolysaccharides From Halophilic Archaeon Haloarcula hispanica

“…pneumoniae , and LPS from P . aeruginosa can also bind with S protein ( Alitongbieke et al, 2020 ; Chiodo et al, 2020 ; Song et al, 2020 ; Bansal et al, 2021 ). These examples clearly demonstrated that glycans with different structural characteristics could prevent SARS-CoV-2 infection, possibly using different mechanisms.…”

Advances in the Prophylaxis of Respiratory Infections by the Nasal and the Oromucosal Route: Relevance to the Fight with the SARS-CoV-2 Pandemic

“…More than 90 natural compounds of the above-mentioned phytochemical categories have shown anti-coronavirus activity [ 142 ]. The latest studies and reviews focus the attention on S-containing polysaccharides ( Chitosan [ 146 ] and semisynthetic derivatives [ 147 ], kappa-, iota-, lambda- Carrageenan [ 148 , 149 , 150 ], Fucoidan [ 150 , 151 , 152 ]), Lactoferrin [ 153 , 154 ], Aloe vera polysaccharides [ 155 ], the flavonoids Hesperidin [ 14 , 156 , 157 ], Hispidulin [ 158 ], Quercetin [ 153 ], Rutin [ 159 ], Resveratrol [ 160 ], the saponin Glycyrrhizin [ 161 ], and the diterpenoid Andrographolide [ 162 , 163 ]. Many of them possess not only the ability to block the adhesin–receptor connection and following viral entry, but are also proven to exhibit antiviral activity due to inhibition of viral replication ( Chitosan and other sulfated polysaccharides [ 145 , 164 , 165 ], Resveratrol [ 166 , 167 ], Aloe vera polysaccharides [ 155 ], Glycyrrhizin [ 168 ], Andrographolide [ 169 ]), inhibition of protein synthesis ( Aloe vera polysaccharides [ 155 ] and Andrographolide [ 169 ]), blocking the viral release and spread ( Andrographolide [ 169 ]), and/or immunomodulatory properties ( Chitosan [ 170 ]).…”

Chitin – A Structural Polysaccharide for Health and Environmental Alimentation

“…More importantly, β-chitosan had been found effective in inhibiting the binding of SARS-CoV-2 with the ACE2 receptor. Even downregulated production of ACE2 receptor in vero E6 cells had been linked with chitosan [76]. Chitosan nanoparticles have been found effective anti-viral drug delivery agents [77].…”