Structural Characterization and AI‐Enhanced Modeling of a Broadly Neutralizing Camelid Antibody Against SARS‐CoV‐2 Variants
Abstract The Omicron variants of SARS‐CoV‐2 are characterized by their high transmissibility and immune evasion. Existing treatments using neutralizing antibodies have shown different effectiveness due to variants with mutations occurring mainly in the RBD and NTD regions. In this study, the functional neutralizing ability of a camelid full‐length antibody (hcAb‐B10) and its corresponding VHH fragment (VHH‐B10) is investigated. Experimental binding studies demonstrated clear recognition and neutralization of Wild‐type (WT) and Omicron variants, but not Delta. Epitope mapping, peptide fragment inhibition, and neutralization studies using pseudovirus expressing respective SARS‐CoV‐2 Spike variants, along with in silico molecular docking studies and AI‐directed structural design, reveal that the B10 antibody interacts effectively with the Spike trimer in a closed position of both WT and Omicron, by targeting the RBD region. This newly generated B10 antibody shows a wide coverage, including the currently dominant Omicron variants, and demonstrates its potential to efficiently neutralize SARS‐CoV‐2.
Authors
- Sławomir Filipek (ORCID: https://orcid.org/0000-0003-3147-3858)
- Stefan Pöhlmann (ORCID: https://orcid.org/0000-0001-6086-9136)
- Rushika Patel (ORCID: https://orcid.org/0000-0002-5801-6182)
- Anandi Krishnan (ORCID: https://orcid.org/0000-0002-0962-2215)
- Ramasamy Paulmurugan (ORCID: https://orcid.org/0000-0001-7155-4738)
- Markus Hoffmann (ORCID: https://orcid.org/0000-0003-4603-7696)
- V. Renugopalakrishnan (ORCID: https://orcid.org/0000-0001-5938-0886)
- Anja Schlör
- Katja Hanack (ORCID: https://orcid.org/0000-0003-2867-689X)
- Chaitanya G. Joshi (ORCID: https://orcid.org/0000-0003-4680-2861)
- Urszula Orzeł (ORCID: https://orcid.org/0000-0002-4002-7764)
- Madhvi N. Joshi (ORCID: https://orcid.org/0000-0003-4102-7114)
- Sourabh Mehta (ORCID: https://orcid.org/0000-0001-5452-1803)
- Dorian Liepmann (ORCID: https://orcid.org/0000-0002-2591-4031)
Institutions
- Northeastern University (US)
- Palo Alto University (US)
- University of Potsdam (DE)
- Leibniz Institute for Astrophysics Potsdam (DE)
- University of Applied Sciences Potsdam (DE)
- German Primate Center (DE)
- Government of Gujarat (IN)
- Center for Systems Biology (US)
- University of Wisconsin–Milwaukee (US)
- University of Warsaw (PL)
- University of Göttingen (DE)
- University of Coimbra (PT)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- Advanced Therapeutics
- Published
- 2025-10-20
- DOI
- https://doi.org/10.1002/adtp.202500244
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- Fundação para a Ciência e a Tecnologia