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

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

doi:10.3389/fchem.2022.871509

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

Front Chem. 2022 Apr 27:10:871509. doi: 10.3389/fchem.2022.871509. eCollection 2022.

Authors

Yueqiang Xu¹, Yan Li², Xin You³, Caixia Pei⁴, Zhuo Wang¹, Siming Jiao¹, Xin Zhao², Xuan Lin¹, Yang Lü⁴, Cheng Jin⁴, George Fu Gao², Jianjun Li¹, Qi Wang², Yuguang Du¹

Affiliations

¹ State Key Laboratory of Biochemical Engineering, National Engineering Research Center for Biotechnology (Beijing), Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA, Institute of Processing and Engineering, Chinese Academy of Sciences, Beijing, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
³ Lung Cancer Translational Medicine Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁴ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Abstract

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 Haloarcula hispanica ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant K_D 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 △HAH_1206 almost completely lost the antiviral activity against SARS-CoV-2. A significant reduction of glucuronic acid (GlcA) and the sulfation level in EPSs of △HAH_1206 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.

Keywords: Haloarcula hispanica; SARS-CoV-2; archaea; exopolysaccharide; sulfated glucuronic acid.