Controlling the SARS-CoV-2 spike glycoprotein conformation.

Journal Article

The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.

Full Text

Duke Authors

Cited Authors

  • Henderson, R; Edwards, RJ; Mansouri, K; Janowska, K; Stalls, V; Gobeil, SMC; Kopp, M; Li, D; Parks, R; Hsu, AL; Borgnia, MJ; Haynes, BF; Acharya, P

Published Date

  • October 2020

Published In

Volume / Issue

  • 27 / 10

Start / End Page

  • 925 - 933

PubMed ID

  • 32699321

Pubmed Central ID

  • 32699321

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

Digital Object Identifier (DOI)

  • 10.1038/s41594-020-0479-4

Language

  • eng

Conference Location

  • United States