A proposed role for the SARS‐CoV‐2 nucleocapsid protein in the formation and regulation of biomolecular condensates

Cascarina, Sean M.; Ross, Eric D.

To date, the recently discovered SARS‐CoV‐2 virus has afflicted >6.9 million people worldwide and disrupted the global economy. Development of effective vaccines or treatments for SARS‐CoV‐2 infection will be aided by a molecular‐level understanding of SARS‐CoV‐2 proteins and their interactions with host cell proteins. The SARS‐CoV‐2 nucleocapsid (N) protein is highly homologous to the N protein of SARS‐CoV, which is essential for viral RNA replication and packaging into new virions. Emerging models indicate that nucleocapsid proteins of other viruses can form biomolecular condensates to spatiotemporally regulate N protein localization and function. Our bioinformatic analyses, in combination with pre‐existing experimental evidence, suggest that the SARS‐CoV‐2 N protein is capable of forming or regulating biomolecular condensates in vivo by interaction with RNA and key host cell proteins. We discuss multiple models, whereby the N protein of SARS‐CoV‐2 may harness this activity to regulate viral life cycle and host cell response to viral infection.