Institut de Biologie StructuraleGrenoble / France

IBS’s contribution to fighting the SARS-CoV-2 Coronavirus

The Institut de Biologie Structurale (IBS) is mobilized to fight the SARS-CoV-2 Coronavirus responsible for the Covid-19 disease. Here is the September 2021 status of the work undertaken by IBS groups :

Spike protein project
since the beginning of April 2020, a concerted action involving several groups of the IBS has started, with the aim of producing the Spike glycoprotein located on the membrane of the SARS-CoV-2 virus. This collective action aims at hindering the virus’ attachment to human cells and the infection and understanding its impact on immune defenses. First result

SARS2NUCLEOPROTEIN Project
M. Blackledge (IBS/FDP group) is coordinating a project to study the molecular role of the viral nucleoprotein in the SARS-Cov-2 replication cycle (identification by NMR of inhibition sites of interactions essential to the viral replication machinery). This has led to the publication of two studies characterising for the first time two important intrinsically disordered viral targets : the nucleoprotein (N) and the N terminal domain of the non-structural protein nsp3.
- 1H, 13C and 15N Backbone chemical shift assignments of the n‑terminal and central intrinsically disordered domains of SARS‑CoV‑2 nucleoprotein. Guseva et al. Biomol NMR Assign. 2021 Oct ;15(2):255-260
- 1H, 13C and 15N backbone chemical shift assignments of SARS‑CoV‑2 nsp3a. Salvi et al. Biomol NMR Assign. 2021 Apr ;15(1):173-176

COVI-COMPLECT project
N. Thielens (IBS/CAID group) coordinates a project to study the role of soluble complement lectins in the pathogenesis of SARS-CoV-2 infection (in collaboration with P. Poignard team of the same group).
- Complement Alternative and Mannose-Binding Lectin Pathway Activation Is Associated With COVID-19 Mortality. Defendi et al. Front Immunol. 2021 Sep 10 ;12:742446

S-VLP project
W. Weissenhorn (IBS/EBEV group) coordinates a vaccination project with synthetic lipid particles coated with trimeric envelope glycoprotein S of SARS-CoV-2.
- Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects Macaques from infection. Sulbaran et al. - Cell Reports Medicine (manuscrit in revision)

CoV-Mime project
P. Fender of the MEM group coordinates a project to develop non-infectious mimics of the surface of SARS-CoV-2 coronavirus on a non-infectious adenovirus nanoparticle with a view to vaccination or antiviral screening.. This project involves the ’Adenovirus’ team led by Pascal Fender and the electron microscopy platform, led by Guy Schoehn (IBS/MEM group).
- Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform. Chevillard et al.

’Vaccine technology against emerging viruses - Prototype on coronavirus’ project
This project conducted by Pascal Fender and Marie-Claire Dagher (MEM groupe, Adenovirus team) aims to develop a new vaccine platform addressing all emerging viruses. A first vaccine eliciting a neutralising response against SARS-CoV2 in animal has already been obtained (collaboration with Pascal Poignard’s team (CAID group)). A paper describing the first results has just been published in BioRxiv and the Adenovirus team is now producing up-to-date vaccines addressing SARS-CoV-2 variants.

AcNT-COVID-19 project
The Poignard team of the CAID group is coordinating a project to develop therapeutic neutralizing antibodies for the treatment and prevention of COVID-19 (isolation of antibodies as therapeutics)

Infectious mechanisms by lectins Project
The M&P group of Franck Fieschi is studying the impact of DC/L-SIGN, L-SECtin receptors and related C-type lectins in SARS-CoV-2 infection.
- DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist. Thépaut et al. PLoS Pathog. 2021 ;17(5):e1009576

Spike-Membrane Project
The Forsyth and Fragnetto teams (Institute Laue Langevin), in collaboration with Franck Fieschi’s group (IBS/M&P), are analyzing by neutron reflectometry the impact of the Spike protein in the interaction of the virus with different membrane or lipid structures.
- SARS-CoV-2 spike protein removes lipids from model membranes and interferes with the capacity of high density lipoprotein to exchange lipids. Correa et al. J Colloid Interface Sci. 2021 Nov 15 ;602:732-739.
- Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry. Luchini et al. Sci Rep. 2021 Jul 21 ;11(1):14867.

Spike-HS project
The SAGAG group of Hugues Lortat-Jacob aims to characterize the interactions of the SARS-CoV-2 Spike protein with the ACE2 receptor and heparan sulfates to design an entry inhibitor.

AM-Cov-Path project
This project focuses on the study of the pathogenesis of SARS-Cov-2 infection in a non-human primate model in order to cover two axes : the therapeutic axis and the prophylactic axis. It is coordinated by Roger Le Grand (IDMIT) with the participation of the Dagger team of the IBS/CAID group.

Pancolin project
The Poignard team of the CAID group, in collaboration with the Grenoble Hospital, is carrying out a follow-up of serology and neutralization on a cohort of patients of the Alpine Arc.

ACTIF project
The Dagger team of the CAID group is collaborating on the development of a sensor based on aptamers that could block the entry of the SARS-cov-2 virus or be used as a diagnostic tool (project sponsor : DCM).

COVISER and COVI3S project
The Dagger team of the CAID group is participating in the follow-up of neutralizing antibody responses over time on a cohort of patients from Lyon hospitals

EpiCOVID project
The Dagger team of the CAID group is involved in the exploration of epigenetic pathways to treat the inflammatory response induced by SARS-CoV-2 (project supported by the Institute for Advanced Biosciences)

Covid-1-NMR Consortium
The Blackledge group (IBS/FDP) is participating in the international Covid19-NMR project, currently uniting research teams from 10 countries in Europe and North and South America. The consortium uses NMR to facilitate the identification of inhibitors of SARS-Cov-2 and to investigate the drugability of different protein and RNA targets. Results are immediately made available to the international community via the consortium web-site. First results :
- Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications. Altincekic et al. Front Mol Biosci. 2021 May 10 ;8:653148->https://pubmed.ncbi.nlm.nih.gov/33475934/].

Protein E project
Project led by V. Gordeliy (IBS/ MEMBRANE group) to study the E protein of SARS-CoV-2

MISC project
In collaboration with scientists and clinicians of the University of Geneva, Romain Vivès form the SAGAG group is studying endothelial glycocalyx glycosaminoglycans (GAGs) degradation in children developing multisystem inflammatory syndrome (MISC) following COVID-19 infection.