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Rational optimization of a human neutralizing antibody of SARS-CoV-2
1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China.
Computers in Biology and Medicine
|June 20, 2021
Summary
Researchers optimized antibody P2B-2F6 to create potent neutralizing antibodies against SARS-CoV-2. These optimized antibodies show higher binding affinity and potential activity against the N501Y variant, aiding COVID-19 therapy development.
Area of Science:
- Immunology
- Virology
- Structural Biology
Background:
- Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic.
- Antibody therapies targeting the SARS-CoV-2 spike protein's receptor-binding domain (RBD) are crucial for patient treatment.
- Blocking the interaction between the viral RBD and human ACE2 receptor inhibits viral entry into host cells.
Purpose of the Study:
- To optimize the neutralizing antibody P2B-2F6 for enhanced binding affinity and potency against SARS-CoV-2.
- To investigate structure-based mutations for improved antibody efficacy.
- To assess the potential of engineered antibodies against emerging SARS-CoV-2 variants, including N501Y.
Main Methods:
- Utilized virtual scanning mutagenesis and molecular dynamics simulations for antibody optimization.
- Isolated and characterized antibody P2B-2F6 from B cells of SARS-CoV-2 infected patients.
- Analyzed binding affinities and structural interactions of antibody mutants with the SARS-CoV-2 RBD.
Main Results:
- Identified two potent P2B-2F6 mutants (H:V106R and H:V106R/H:P107Y) with significantly higher binding affinities to the SARS-CoV-2 RBD.
- Observed that polar interactions and an enhanced hydrogen-bonding network at paratope residues 106 and 107 contribute to increased affinity.
- Demonstrated potential neutralizing activity of the optimized antibodies against the N501Y SARS-CoV-2 variant.
Conclusions:
- Structure-based optimization can yield antibodies with superior affinity and neutralizing capacity.
- The developed antibody mutants offer promising therapeutic candidates against SARS-CoV-2, including concerning variants.
- This research provides a framework for designing next-generation antibody therapies for COVID-19.
