SARS-CoV-2 S Glycoprotein Stabilization Strategies

Author:

Pedenko Borys1,Sulbaran Guidenn1,Guilligay Delphine1,Effantin Gregory1ORCID,Weissenhorn Winfried1ORCID

Affiliation:

1. University Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), 38000 Grenoble, France

Abstract

The SARS-CoV-2 pandemic has again shown that structural biology plays an important role in understanding biological mechanisms and exploiting structural data for therapeutic interventions. Notably, previous work on SARS-related glycoproteins has paved the way for the rapid structural determination of the SARS-CoV-2 S glycoprotein, which is the main target for neutralizing antibodies. Therefore, all vaccine approaches aimed to employ S as an immunogen to induce neutralizing antibodies. Like all enveloped virus glycoproteins, SARS-CoV-2 S native prefusion trimers are in a metastable conformation, which primes the glycoprotein for the entry process via membrane fusion. S-mediated entry is associated with major conformational changes in S, which can expose many off-target epitopes that deviate vaccination approaches from the major aim of inducing neutralizing antibodies, which mainly target the native prefusion trimer conformation. Here, we review the viral glycoprotein stabilization methods developed prior to SARS-CoV-2, and applied to SARS-CoV-2 S, in order to stabilize S in the prefusion conformation. The importance of structure-based approaches is highlighted by the benefits of employing stabilized S trimers versus non-stabilized S in vaccines with respect to their protective efficacy.

Funder

ANR

the “Institut Universitaire de France”

the European Union’s Horizon 2020

FRISBI

the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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