A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• Antibodies against the SARS-CoV-2 nucleocapsid (N) protein are common after infection, but their function remains largely uncharacterized.
• Understanding N protein-specific antibodies is crucial, as they may play a role in COVID-19 pathogenesis.

Purpose of the Study:

• To isolate and functionally characterize monoclonal antibodies (mAbs) targeting the SARS-CoV-2 N protein.
• To investigate the structural basis of N protein recognition by mAbs.
• To assess the impact of anti-N protein mAbs on complement activation.

Main Methods:

• Isolation and profiling of 32 N protein-specific monoclonal antibodies (mAbs) from a COVID-19 convalescent patient.
• Co-complex structural analysis of the N protein RNA binding domain with a high-affinity mAb (nCoV396).
• Virus-free complement hyperactivation assays to evaluate mAb function.

Main Results:

• A panel of 32 N protein-specific mAbs was generated, with dominant responses observed in a rapid recovery patient.
• Structural studies revealed epitope details and allosteric regulation of the N protein upon binding with mAb nCoV396.
• mAb nCoV396 demonstrated the ability to inhibit N protein-induced complement hyperactivation.

Conclusions:

• The study identified functional anti-N protein mAbs, including nCoV396, which can modulate complement activation.
• These findings provide a foundation for developing therapeutic strategies targeting N protein-mediated immune responses in COVID-19.