Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding
Panpan Zhou1,2, Meng Yuan3, Yuexiu Zhang4,5
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.
Plos Pathogens
|August 7, 2026
Summary
Researchers engineered a human antibody (CC65.1) to neutralize multiple betacoronaviruses, including MERS-CoV. This breakthrough enhances pandemic preparedness by developing broadly protective antibody countermeasures against diverse viral threats.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Broadly neutralizing antibodies (bnAbs) targeting conserved regions of the betacoronavirus spike protein are crucial for pan-betacoronavirus protection.
- Developing effective countermeasures against diverse betacoronaviruses remains a key challenge for pandemic preparedness.
Purpose of the Study:
- To isolate and characterize human monoclonal antibodies targeting conserved regions of the betacoronavirus spike protein.
- To engineer existing antibodies for enhanced binding affinity and neutralization breadth against divergent betacoronaviruses.
Main Methods:
- Isolation of a human monoclonal antibody (CC65.1) from a SARS-CoV-2 convalescent donor.
- Utilizing directed evolution to enhance antibody binding affinity.
- High-resolution structural analysis of antibody-epitope interactions.
Main Results:
- CC65.1 targets the conserved S2 stem helix region and neutralizes sarbecoviruses, including SARS-CoV-2.
- Engineered variants of CC65.1 acquired MERS-CoV-neutralizing activity through enhanced binding affinity.
- Structural analysis identified key mutations responsible for improved binding and epitope engagement.
Conclusions:
- In vitro affinity maturation can expand the neutralization breadth of stem-helix-targeting antibodies across divergent betacoronaviruses.
- Engineered bnAbs targeting conserved regions offer a promising strategy for broad betacoronavirus countermeasures.
- This work provides a method for achieving cross-lineage neutralization against betacoronaviruses.
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