An essential interaction folds the nucleoprotein of the SARS-CoV-2 virus around its viral partner nsp3a

While vaccines target the molecular mechanisms responsible for infection of the cell via the Spike protein, it is equally important to target the viral replication machinery in patients already infected with the virus.
Researchers at the IBS (Protein Dynamics and Flexibility by NMR Group) characterised the nucleoprotein (N) of SARS-CoV-2, the most abundant protein produced by the virus. This protein has numerous functions that are essential for viral infection, including protection of the viral genome against the intracellular host immune system.
This natural target for the development of antiviral inhibitors comprises long intrinsically disordered domains which confer a high degree of flexibility – essential for its biochemical activity – but which also renders it particularly difficult to characterize using classical structural biology. IBS researchers used NMR (nuclear magnetic resonance) spectroscopy - used this technique to determine the structure and dynamics of the protein N and to describe its interaction with the viral partner nsp3a – an interaction that is essential for viral function.
The interaction implicates two distinct “linear motifs” within the central disordered domain of the protein N, which wrap the disordered domain around the partner nsp3a. This results in a substantial collapse of the dimensions of N, forming a highly compact, but still dynamic molecular assembly, which is also shown to regulate the ability to bind viral RNA.
The first molecular description of an essential interaction between two proteins from SARS-CoV-2 provides new insight which could inspire innovative inhibitory strategies to combat COVID-19. Press release (currently only available in French).

The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a, Science Advances;8(3):eabm4034. doi: 10.1126/sciadv.abm4034

Contact: Martin Blackledge (IBS/Protein Dynamics and Flexibility by NMR Group)