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

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

doi:10.1016/j.isci.2024.108976

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

iScience. 2024 Jan 19;27(2):108976. doi: 10.1016/j.isci.2024.108976. eCollection 2024 Feb 16.

Authors

Youngchang Kim^{1

2}, Natalia Maltseva^{1

2}, Christine Tesar^{1

2}, Robert Jedrzejczak^{1

2}, Michael Endres^{1

2}, Heng Ma³, Haley L Dugan⁴, Christopher T Stamper⁴, Changsoo Chang^{1

2}, Lei Li⁴, Siriruk Changrob⁴, Nai-Ying Zheng⁴, Min Huang⁴, Arvind Ramanathan³, Patrick Wilson⁵, Karolina Michalska^{1

2}, Andrzej Joachimiak^{1

2

4}

Affiliations

¹ Center for Structural Biology of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60367, USA.
² Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Lemont, IL 60439, USA.
³ Data Science and Learning Division, Argonne National Laboratory, Lemont, IL 60439, USA.
⁴ Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60367, USA.
⁵ Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10021, USA.

Abstract

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 (NP^RBD) 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 NP^RBD were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NP^RBD 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.

Keywords: Biochemistry; Immunology; Structural biology.

Abstract

Grants and funding