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

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

doi:10.1016/j.isci.2024.108976

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

Journal Article · Fri Jan 19 00:00:00 UTC 2024 · iScience

DOI: https://doi.org/10.1016/j.isci.2024.108976 · OSTI ID:2470243

Kim, Youngchang ^[1]; Maltseva, Natalia ^[1]; Tesar, Christine ^[1]; Jedrzejczak, Robert ^[1]; Endres, Michael ^[1]; Ma, Heng ^[2]; Dugan, Haley L. ^[3]; Stamper, Christopher T. ^[3]; Chang, Changsoo ^[1]; Li, Lei ^[3]; Changrob, Siriruk ^[3]; Zheng, Nai-Ying ^[3]; Huang, Min ^[3]; Ramanathan, Arvind ^[2]; Wilson, Patrick ^[4]; Michalska, Karolina ^[1];

^[1]

Univ. of Chicago, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)
Argonne National Laboratory (ANL), Argonne, IL (United States)
Univ. of Chicago, IL (United States)
Cornell Univ., Ithaca, NY (United States). Weill Medical College

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); U.S. Department of Health and Human Services (HHS); USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 2470243

Journal Information:: iScience, Journal Name: iScience Journal Issue: 2 Vol. 27; ISSN 2589-0042

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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

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