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

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 SARSCoV-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.