AUTHOR=Xu Yueqiang , Li Yan , You Xin , Pei Caixia , Wang Zhuo , Jiao Siming , Zhao Xin , Lin Xuan , Lü Yang , Jin Cheng , Gao George Fu , Li Jianjun , Wang Qi , Du Yuguang 

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

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.871509

DOI=10.3389/fchem.2022.871509

ISSN=2296-2646

ABSTRACT=<p>The pandemic caused by SARS-CoV-2 is the most widely spread disease in the 21st century. Due to the continuous emergence of variants across the world, it is necessary to expand our understanding of host–virus interactions and explore new agents against SARS-CoV-2. In this study, it was found exopolysaccharides (EPSs) from halophilic archaeon <italic>Haloarcula hispanica</italic> ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant K<sub>D</sub> of 2.23 nM, block the binding of spike protein to Vero E6 and bronchial epithelial BEAS-2B cells, and inhibit pseudovirus infection. However, EPSs from the gene deletion mutant <italic>△HAH_1206</italic> almost completely lost the antiviral activity against SARS-CoV-2. A significant reduction of glucuronic acid (GlcA) and the sulfation level in EPSs of <italic>△HAH_1206</italic> was clearly observed. Our results indicated that sulfated GlcA in EPSs is possible for a main structural unit in their inhibition of binding of SARS-CoV-2 to host cells, which would provide a novel antiviral mechanism and a guide for designing new agents against SARS-CoV-2.</p>