Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication

Area of Science:

• Virology and Molecular Biology
• Biophysics and Biomolecular Condensates

Background:

• Retroviruses and coronaviruses have caused devastating pandemics, highlighting the need for effective antiviral strategies.
• Nucleocapsid proteins of these viruses are essential for RNA binding, genome packaging, and viral replication.
• These proteins are recognized as critical drug targets due to their central roles in the viral life cycle.

Purpose of the Study:

• To review fundamental studies on retroviral and coronavirus nucleocapsid proteins.
• To elucidate the role of liquid-liquid phase separation (LLPS) in viral replication.
• To explore therapeutic targeting of nucleocapsid protein condensates and discuss methodological advancements.

Main Methods:

• Review of existing literature on nucleocapsid protein structure-function relationships.
• Analysis of studies investigating the biophysical properties of nucleocapsid proteins, particularly LLPS.
• Examination of research on therapeutic strategies targeting viral condensates.

Main Results:

• Nucleocapsid proteins possess intrinsic abilities to undergo LLPS, forming dynamic condensates.
• These LLPS-driven condensates are integral to various stages of viral replication, including RNA packaging.
• LLPS of nucleocapsid proteins influences viral assembly and infectivity.

Conclusions:

• Liquid-liquid phase separation is a key mechanism by which nucleocapsid proteins contribute to viral replication.
• Targeting these phase-separated condensates represents a novel therapeutic avenue for controlling retroviral and coronavirus infections.
• Further research into LLPS mechanisms and condensate targeting is crucial for developing next-generation antivirals.