Issue 35, 2024

Water–glycan interactions drive the SARS-CoV-2 spike dynamics: insights into glycan-gate control and camouflage mechanisms

Abstract

To develop therapeutic strategies against COVID-19, we introduce a high-resolution all-atom polarizable model capturing many-body effects of protein, glycan, solvent, and membrane components in SARS-CoV-2 spike protein open and closed states. Employing μs-long molecular dynamics simulations powered by high-performance cloud-computing and unsupervised density-driven adaptive sampling, we investigated the differences in bulk-solvent–glycan and protein–solvent–glycan interfaces between these states. We unraveled a sophisticated solvent–glycan polarization interaction network involving the N165/N343 glycan-gate patterns that provide structural support for the open state and identified key water molecules that could potentially be targeted to destabilize this configuration. In the closed state, the reduced solvent polarization diminishes the overall N165/N343 dipoles, yet internal interactions and a reorganized sugar coat stabilize this state. Despite variations, our glycan–solvent accessibility analysis reveals the glycan shield capability to conserve constant interactions with the solvent, effectively camouflaging the virus from immune detection in both states. The presented insights advance our comprehension of viral pathogenesis at an atomic level, offering potential to combat COVID-19.

Graphical abstract: Water–glycan interactions drive the SARS-CoV-2 spike dynamics: insights into glycan-gate control and camouflage mechanisms

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Article information

Article type
Edge Article
Submitted
02 jul 2024
Accepted
22 aug 2024
First published
23 aug 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 14177-14187

Water–glycan interactions drive the SARS-CoV-2 spike dynamics: insights into glycan-gate control and camouflage mechanisms

M. Blazhynska, L. Lagardère, C. Liu, O. Adjoua, P. Ren and J. Piquemal, Chem. Sci., 2024, 15, 14177 DOI: 10.1039/D4SC04364B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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