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

• Published in: iScience Vol. 27; no. 2; p. 108976
• Main Authors: Kim, Youngchang, Maltseva, Natalia, Tesar, Christine, Jedrzejczak, Robert, Endres, Michael, Ma, Heng, Dugan, Haley L., Stamper, Christopher T., Chang, Changsoo, Li, Lei, Changrob, Siriruk, Zheng, Nai-Ying, Huang, Min, Ramanathan, Arvind, Wilson, Patrick, Michalska, Karolina, Joachimiak, Andrzej
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-02-2024; Elsevier
• Subjects: BASIC BIOLOGICAL SCIENCES; Biochemistry; Immunology; Science & Technology - Other Topics; Structural biology; Biochemistry; Structural biology; Immunology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108976

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.
[Display omitted]
•Structures of SARS-CoV-2 nucleocapsid RNA-binding domain, NPRBD, show key epitopes•The mAbs-NPRBD complexes reveal distinct CDRs recognizing divergent epitopes•The models of nucleocapsid dimer and the RNA complexes reveal key mutations•Simulations show how antibody disrupts the natural dynamic fluctuation of nucleocapsid
Biochemistry; Immunology; Structural biology