Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies

• Published in: iScience
• Main Authors: Youngchang Kim, Natalia Maltseva, Christine Tesar, Robert Jedrzejczak, Michael Endres, Heng Ma, Haley L. Dugan, Christopher T. Stamper, Changsoo Chang, Lei Li, Siriruk Changrob, Nai-Ying Zheng, Min Huang, Arvind Ramanathan, Patrick Wilson, Karolina Michalska, Andrzej Joachimiak
• Format: Article
• Language: English
• Published: Elsevier 2024-02-01
• Subjects: Biochemistry; Immunology; Structural biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004224001974

Summary: Coronavirus nucleocapsid protein (NP) of SARS-CoV-2 plays a central role in many functions important for virus proliferation including packaging and protecting genomic RNA. The protein shares sequence, structure, and architecture with nucleocapsid proteins from betacoronaviruses. The N-terminal domain (NPRBD) binds RNA and the C-terminal domain is responsible for dimerization. After infection, NP is highly expressed and triggers robust host immune response. The anti-NP antibodies are not protective and not neutralizing but can effectively detect viral proliferation soon after infection. Two structures of SARS-CoV-2 NPRBD were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NPRBD complexes with human mAbs were isolated using an antigen-bait sorting. Complexes revealed a distinct complement-determining regions and unique sets of epitope recognition. This may assist in the early detection of pathogens and designing peptide-based vaccines. Mutations that significantly increase viral load were mapped on developed, full length NP model, likely impacting interactions with host proteins and viral RNA.