Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Découvertes et avancées | Scientific result | Virus | Structural biology | Diagnosis and innovative treatment
Researchers from the CEA-Irig (IBS), Grenoble Alpes University, the CNRS and the ESRF have described for the first time an essential interaction between two SARS-CoV-2 proteins that could inspire a new therapeutic strategy against COVID-19.
While vaccines target the entry of the virus into the cell via the spike protein, it would be interesting to also be able to target the replication machinery of the virus, so as to treat individuals already infected.
This is why CEA-Irig researchers (at the Institute of Structural Biology in Grenoble) have chosen to study the nucleoprotein N of SARS-CoV-2, one of the virus's most abundant proteins. This nucleoprotein is important to several vital functions:
This natural target for developing an antiviral treatment contains long, disordered regions that give it great flexibility – the key to its biochemical action – but also make it extremely challenging to study. For this reason, the protein remains poorly characterized outside of its structured domains.
The IBS researchers – experts in NMR (nuclear magnetic resonance) spectroscopy, which gives them access to atomic resolution even in the case of very dynamic systems – have succeeded in describing:
This interaction, which places the N protein at the site of viral genome production, is crucial for virus replication. It involves two "linear motifs" of the central disordered domain of N, which envelop the nsp3a protein by folding the disordered domain around the partner. This results in a substantial reduction in the volume of N. The two proteins therefore form a very compact molecular assembly that can regulate the essential interaction of N with the viral RNA. This work provides insight into the mechanism of virus replication and opens the way to the development of new strategies against COVID-19, for example by inhibiting this important interaction for viral replication.
The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a, Science Advances
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.