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Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2

Tamina Park, Sang-Yeop LeeiD, Seil KimiD, Mi Jeong KimiD, Hong Gi KimiD, Sangmi Jun, Seung Il KimiD, Bum‐Tae KimiD, Edmond Changkyun ParkiD, Daeui ParkiD

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Abstract

Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the {beta}-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2.

Abstract summary

Claude Opus 5.5 · xhigh effort · 18 Oct 2026 · from the abstract

Docking known coronavirus neutralizing antibodies onto SARS-CoV-2 spike predicts CR3022 binds it more tightly than SARS-CoV spike; two receptor-binding-domain insertions sit near ACE2-contacting residues.

With no SARS-CoV-2 therapeutic in hand, one shortcut is to ask whether antibodies raised against related coronaviruses still recognise its spike protein. This work compares the SARS-CoV-2 spike receptor-binding domain with SARS-CoV and bat SARS-related viruses, contrasts the epitopes of SARS-CoV and MERS-CoV antibodies, and ranks existing antibodies by predicted affinity, entirely computationally.

Key results

  1. SuggestedSequence comparison places two main differences in the receptor-binding domain of the SARS-CoV-2 spike relative to SARS-CoV and bat SARS-related coronaviruses, and these inserted stretches lie close to the residues that contact human ACE2.

    Reported from spike sequence alignment; the abstract gives no residue positions, insertion lengths, distances to the ACE2 interface or sequence identities. · Abstract

  2. SuggestedNeutralizing antibodies against SARS-CoV are reported to recognise conformational epitopes, whereas MERS-CoV antibodies share a linear epitope that forms a beta-sheet in the MERS-CoV spike; that region is absent from the SARS-CoV-2 spike.

    Epitope analysis across the two antibody sets; no epitope coordinates, antibody counts or structural evidence are given in the abstract. · Abstract

  3. SuggestedIn antibody-antigen docking, the human antibody CR3022 is predicted to bind the SARS-CoV-2 spike with greater affinity than the SARS-CoV spike, while the mouse antibodies F26G19 and D12 are predicted to bind the SARS-CoV spike strongly.

    Docking simulation only, with the CR3022 result stated as a possibility; no docking scores, binding energies or experimental affinity measurements are reported. · Abstract

Methods, data and reproducibility

Bioinformatic study combining sequence comparison of the SARS-CoV-2 spike with SARS-CoV and bat SARS-related coronavirus spike proteins, analysis of the epitopes used by known SARS-CoV and MERS-CoV neutralizing antibodies, and antibody-antigen docking simulations to predict and rank binding affinities against the SARS-CoV-2 spike.

  • Spike protein sequences compared across the three virus groups · SARS-CoV-2, SARS-CoV, bat SARS-related coronaviruses
  • Epitopes of known neutralizing antibodies against SARS-CoV and MERS-CoV
  • Neutralizing antibodies used in docking, including human CR3022 and mouse F26G19 and D12 · human and mouse antibodies
Limitations (2)
  • Every result is a prediction: no binding measurement, neutralization assay or experimental structure is reported, and the abstract lists no docking scores or energies behind the affinity ranking. · noted in this summary
  • The docking pipeline is not benchmarked against antibody-antigen pairs with known measured affinities, so there is no basis in the abstract for judging how reliable the ranking is. · noted in this summary

Read this if you triage cross-reactive coronavirus antibodies in silico, or want an early comparison of the SARS-CoV-2 spike receptor-binding domain and antibody epitopes against SARS-CoV and MERS-CoV.

Citations
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