Revisiting the interaction between complement lectin pathway protease MASP-2 and SARS-CoV-2 nucleoprotein.

Area of Science:

• Immunology
• Virology
• Biochemistry

Background:

• Complement activation contributes to severe SARS-CoV-2 pathogenesis via inflammatory responses.
• The lectin complement pathway, initiated by mannose-binding lectin (MBL) recognizing the Spike glycoprotein, is crucial for innate antiviral defense.
• Previous studies suggested SARS-CoV-2 nucleoprotein (N) interaction with MASP-2 potentiates the lectin pathway.

Purpose of the Study:

• To re-investigate the interaction between SARS-CoV-2 nucleoprotein (N) and mannose-binding lectin-associated serine protease 2 (MASP-2).
• To clarify the role of N protein in MBL-mediated lectin pathway activation.
• To explore potential functional significance of N protein and MASP-2 interaction in SARS-CoV-2 infection.

Main Methods:

• Investigated interactions between SARS-CoV-2 N protein (bacterial or mammalian origin) and full-length or catalytic domain of MASP-2 (active or proenzyme forms).
• Assessed N protein binding to MASP-2 and its role in MBL-mediated lectin pathway activation.
• Analyzed proteolysis of N protein upon incubation with MASP-2.

Main Results:

• Confirmed N protein binding to proenzyme MASP-2 but not to the MASP-2 catalytic domain.
• Found no evidence for N protein involvement in MBL-mediated lectin pathway activation.
• Observed proteolysis of the SARS-CoV-2 N protein when incubated with MASP-2.

Conclusions:

• The SARS-CoV-2 nucleoprotein does not appear to potentiate MBL-initiated lectin pathway activation.
• N protein interacts with proenzyme MASP-2, leading to its own proteolysis.
• The functional significance of N protein proteolysis by MASP-2 in SARS-CoV-2 infected patients requires further investigation.