Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

Bingqian Li; Lin Wang; Huan Ge; Xianglei Zhang; Penxuan Ren; Yu Guo; Wuyan Chen; Jie Li; Wei Zhu; Wenzhang Chen; Lili Zhu; Fang Bai

doi:10.3389/fchem.2021.659764

Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

Front Chem. 2021 Jul 22:9:659764. doi: 10.3389/fchem.2021.659764. eCollection 2021.

Authors

Bingqian Li^{1

2}, Lin Wang¹, Huan Ge³, Xianglei Zhang¹, Penxuan Ren¹, Yu Guo⁴, Wuyan Chen⁵, Jie Li⁵, Wei Zhu¹, Wenzhang Chen¹, Lili Zhu³, Fang Bai¹

Affiliations

¹ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
² Department of Chemistry, Imperial College London, London, United Kingdom.
³ State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
⁴ State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
⁵ National Center for Protein Science Shanghai, Shanghai, China.

Abstract

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

Keywords: RBD domain; SARS-CoV-2; receptor; sialic acid; spike protein.