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Elucidating important structural features for the binding affinity of spike - SARS-CoV-2 neutralizing antibody
Divya Sharma1, Puneet Rawat1, Vani Janakiraman2
1Protein Bioinformatics Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.
Abstract:
The coronavirus disease 2019 (COVID-19) has affected the lives of millions of people around the world. In an effort to develop therapeutic interventions and control the pandemic, scientists have isolated several neutralizing antibodies against SARS-CoV-2 from the vaccinated and convalescent individuals. These antibodies can be explored further to understand SARS-CoV-2 specific antigen-antibody interactions and biophysical parameters related to binding affinity, which can be utilized to engineer more potent antibodies for current and emerging SARS-CoV-2 variants. In the present study, we have analyzed the interface between spike protein of SARS-CoV-2 and neutralizing antibodies in terms of amino acid residue propensity, pair preference, and atomic interaction energy. We observed that Tyr residues containing contacts are highly preferred and energetically favorable at the interface of spike protein-antibody complexes. We have also developed a regression model to relate the experimental binding affinity for antibodies using structural features, which showed a correlation of 0.93. Moreover, several mutations at the spike protein-antibody interface were identified, which may lead to immune escape (epitope residues) and improved affinity (paratope residues) in current/emerging variants. Overall, the work provides insights into spike protein-antibody interactions, structural parameters related to binding affinity and mutational effects on binding affinity change, which can be helpful to develop better therapeutics against COVID-19.
Insights
Scientists analyzed the SARS-CoV-2 spike protein-antibody interface, finding Tyr residues crucial for binding affinity. This research aids in developing improved COVID-19 therapeutics against evolving variants.
Area of Science:
- Structural Biology
- Immunology
- Computational Biology
Background:
- The COVID-19 pandemic necessitates the development of effective therapeutics, including neutralizing antibodies targeting SARS-CoV-2.
- Understanding antigen-antibody interactions is key to engineering potent antibodies against current and emerging viral variants.
Purpose of the Study:
- To analyze the structural features of the SARS-CoV-2 spike protein-antibody interface.
- To identify key amino acid residues and interactions influencing binding affinity.
- To develop a predictive model for antibody binding affinity and explore mutational effects.
Main Methods:
- Analysis of amino acid residue propensity, pair preference, and atomic interaction energy at the spike protein-antibody interface.
- Development of a regression model correlating structural features with experimental binding affinity.
- Identification of mutations at the interface and their potential impact on immune escape and affinity.
Main Results:
- Tyrosine (Tyr) residues were identified as highly preferred and energetically favorable at the spike protein-antibody interface.
- A regression model accurately predicted binding affinity with a correlation of 0.93 using structural features.
- Specific mutations were linked to potential immune escape (epitope) and altered binding affinity (paratope).
Conclusions:
- Insights into spike protein-antibody interactions provide a foundation for designing enhanced COVID-19 therapeutics.
- Structural parameters and mutational effects on binding affinity are critical for developing antibodies effective against SARS-CoV-2 variants.
- This work facilitates the engineering of more potent antibodies for pandemic control.
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