Phase Separation by the SARS-CoV-2 Nucleocapsid Protein: Consensus and Open Questions

In response to the recent SARS-CoV-2 pandemic, a number of labs across the world have re-allocated their time and resources to better our understanding of the virus. For some viruses, including SARS-CoV-2, viral proteins can undergo phase separation: a biophysical process often related to the partitioning of protein and RNA into membraneless organelles in vivo. In this review we discuss emerging observations of phase separation by the SARS-CoV-2 nucleocapsid (N) protein – an essential viral protein required for viral replication – and the possible in vivo functions that have been proposed for N-protein phase separation, including viral replication, viral genomic RNA packaging, and modulation of host-cell response to infection. Additionally, since a relatively large number of studies examining SARS-CoV-2 N-protein phase separation have been published in a short span of time, we take advantage of this situation to compare results from similar experiments across studies. Our evaluation highlights potential strengths and pitfalls of drawing conclusions from a single set of experiments, as well as the value of publishing overlapping scientific observations performed simultaneously by multiple labs.