iScience . The effect of N- glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor

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iScience


. 2021 Oct 13;103272.
doi: 10.1016/j.isci.2021.103272. Online ahead of print.
The effect of N- glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor


Chuncui Huang ^{1 2} , Zeshun Tan ^{1 3} , Keli Zhao ^{1 3} , Wenjun Zou ^{1 3} , Hui Wang ^{4 3} , Huanyu Gao ¹ , Shiwei Sun ^{4 3} , Dongbo Bu ^{4 3} , Wengang Chai ⁵ , Yan Li ^{1 3 2}



Affiliations

• PMID: 34661088
• PMCID: PMC8513389
• DOI: 10.1016/j.isci.2021.103272

Abstract

The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hinderance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.

Keywords: Binding affinity; N-glycosylation; S1 protein; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); Spike protein.