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SARS-CoV-2 neutralizing antibody epitopes are overlapping and highly mutated which raises the chances of escape variants and requires development of broadly reactive vaccines
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  • V. Stalin Raj,
  • Jeswin Joseph,
  • Sukhada Darpe,
  • Grishma Kulkarni
V. Stalin Raj
Indian Institute of Science Education and Research Thiruvananthapuram

Corresponding Author:[email protected]

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Jeswin Joseph
Indian Institute of Science Education and Research Thiruvananthapuram
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Sukhada Darpe
Indian Institute of Science Education and Research Thiruvananthapuram
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Grishma Kulkarni
Indian Institute of Science Education and Research Thiruvananthapuram
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Abstract

The rapid adaptation of SARS-CoV-2 within the host species and the increased viral transmission triggered the evolution of different SARS-CoV-2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS-CoV-2, the ongoing surge in the number of SARS-CoV-2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS-CoV-2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor-binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N-terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4-10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co-evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS-CoV-2 variants. Further, vaccines inducing both humoral and cell-mediated immune responses might prevent the escape of SARS-CoV-2 variants from neutralizing antibodies.
10 Nov 2022Submitted to PROTEINS: Structure, Function, and Bioinformatics
11 Nov 2022Submission Checks Completed
11 Nov 2022Assigned to Editor
11 Nov 2022Review(s) Completed, Editorial Evaluation Pending
22 Nov 2022Reviewer(s) Assigned
01 Feb 2023Editorial Decision: Revise Minor
07 Feb 20231st Revision Received
08 Feb 2023Submission Checks Completed
08 Feb 2023Assigned to Editor
08 Feb 2023Review(s) Completed, Editorial Evaluation Pending
18 Feb 2023Reviewer(s) Assigned
28 Feb 2023Editorial Decision: Accept