Rxivist logo

Inhibition of SARS-CoV-2 viral entry in vitro upon blocking N- and O-glycan elaboration

By Qi Yang, Thomas A Hughes, Anju Kelkar, Xinheng Yu, Kai Cheng, Sheldon J. Park, Wei-Chiao Huang, Jonathan F. Lovell, Sriram Neelamegham

Posted 15 Oct 2020
bioRxiv DOI: 10.1101/2020.10.15.339838 (published DOI: 10.7554/eLife.61552)

The Spike protein of SARS-CoV-2, its receptor binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19. ### Competing Interest Statement A provisional patent related to this work has been filed by Q.Y., T.A.H, A.K. and S.N.

Download data

  • Downloaded 544 times
  • Download rankings, all-time:
    • Site-wide: 59,997
    • In biochemistry: 1,576
  • Year to date:
    • Site-wide: 44,537
  • Since beginning of last month:
    • Site-wide: 66,389

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News