Condensates of SARS-CoV-2 Nucleoprotein on Viral RNA and Their Small Molecule Modulators

Abstract

Several types of biopolymers undergo liquid-liquid phase separation (form condensates) in aqueous solutions, and this phenomenon has been characterized in detail for proteins with intrinsically disordered regions. One example of such proteins is the nucleocapsid (N) protein of the severe acute respiratory syndrome coronavirus 2. In this review, we analyzed available data on N-protein separation in the presence of viral RNA. Particular attention was paid to transient contacts within the condensates and the N-protein/RNA fragments that form these contacts. We also discussed the presumed role of the condensates in the SARS-CoV-2 life cycle and summarized their influence on the host protective machinery. Finally, we commented on the possibility of regulating the viral condensates using synthetic or native small molecules (phase separation modulators), which can provide a new option in the design of antiviral agents.