Abstract

The SARS-CoV-2 nucleocapsid protein, or N-protein, is a structural protein that plays an important role in the SARS-CoV-2 life cycle. The N-protein takes part in the regulation of viral RNA replication and drives highly specific packaging of full-length genomic RNA prior to virion formation. One regulatory mechanism that is proposed to drive the switch between these two operating modes is the phosphorylation state of the N-protein. Here, we assess the dynamic behavior of phosphorylated and non-phosphorylated versions of the N-protein homodimer through atomistic molecular dynamics simulations. We show that the introduction of phosphorylation yields a more dynamic protein structure and we find that the effect of phosphorylation on the interaction between the N-protein and RNA depends on the involved RNA sequence. Our results provide detailed molecular insights into N-protein dynamics and corroborate the hypothesis that phosphorylation of the N-protein can serve as a regulatory mechanism which determines N-protein function.