Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS-CoV-2 nucleocapsid protein and its...

Area of Science:

• Virology
• Immunology
• Pathophysiology

Background:

• SARS-CoV-2 infection causes COVID-19 with varied severity, from asymptomatic to critical illness.
• A significant portion of infected individuals (~40%) develop long COVID, experiencing persistent symptoms beyond 12 weeks.
• Long COVID is associated with persistent low-grade inflammation and cytokine markers, with no effective treatments currently available.

Purpose of the Study:

• To review the basic studies of the coronavirus nucleocapsid protein (N protein).
• To highlight the N protein's ability to undergo liquid-liquid phase separation (LLPS).
• To propose a novel hypothesis linking N protein LLPS to the pathogenesis of long COVID.

Main Methods:

• Review of existing literature on SARS-CoV-2, COVID-19, and long COVID.
• Examination of studies focusing on the structure and function of the coronavirus nucleocapsid protein.
• Analysis of research on liquid-liquid phase separation in viral proteins.

Main Results:

• The coronavirus nucleocapsid protein plays a crucial role in viral replication and RNA binding.
• The nucleocapsid protein exhibits the property of liquid-liquid phase separation.
• A subset of long COVID patients shows persistent inflammation and specific cytokine profiles.

Conclusions:

• The ability of the nucleocapsid protein to undergo liquid-liquid phase separation is a key characteristic.
• This LLPS capability is hypothesized to contribute to the development or persistence of long COVID.
• This hypothesis opens new avenues for understanding and potentially treating long COVID.