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Review of COVID-19 Antibody Therapies
Jiahui Chen1, Kaifu Gao1, Rui Wang1
1Department of Mathematics, Michigan State University, East Lansing, Michigan 48824, USA;
Abstract:
In the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop; they are as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and they have thus attracted much attention in the past few months. This article reviews seven existing antibodies for neutralizing SARS-CoV-2 with 3D structures deposited in the Protein Data Bank (PDB). Five 3D antibody structures associated with the SARS-CoV spike (S) protein are also evaluated for their potential in neutralizing SARS-CoV-2. The interactions of these antibodies with the S protein receptor-binding domain (RBD) are compared with those between angiotensin-converting enzyme 2 and RBD complexes. Due to the orders of magnitude in the discrepancies of experimental binding affinities, we introduce topological data analysis, a variety of network models, and deep learning to analyze the binding strength and therapeutic potential of the 14 antibody-antigen complexes. The current COVID-19 antibody clinical trials, which are not limited to the S protein target, are also reviewed.
Insights
Antibody therapies targeting the SARS-CoV-2 spike protein offer specific COVID-19 treatment options. Advanced computational methods analyze 14 antibody-antigen complexes to assess therapeutic potential.
Area of Science:
- Structural biology
- Immunology
- Computational biology
Background:
- The COVID-19 pandemic necessitates rapid development of effective therapies.
- Antibody therapies present a promising avenue due to their specificity and ease of development compared to small-molecule drugs.
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets the ACE2 receptor via its spike (S) protein.
Purpose of the Study:
- To review existing neutralizing antibodies against SARS-CoV-2 with available 3D structures.
- To evaluate the potential of SARS-CoV antibodies for cross-neutralization against SARS-CoV-2.
- To analyze the binding interactions and therapeutic potential of antibody-antigen complexes using advanced computational methods.
Main Methods:
- Review of seven SARS-CoV-2 neutralizing antibodies and five SARS-CoV antibodies with deposited 3D structures in the Protein Data Bank (PDB).
- Comparative analysis of antibody-S protein receptor-binding domain (RBD) interactions against angiotensin-converting enzyme 2 (ACE2)-RBD interactions.
- Application of topological data analysis, network models, and deep learning to analyze binding affinities and therapeutic potential of 14 antibody-antigen complexes.
Main Results:
- Identified and structurally analyzed seven SARS-CoV-2 neutralizing antibodies and five SARS-CoV antibodies.
- Compared binding interactions of antibodies with the SARS-CoV-2 RBD to ACE2-RBD interactions.
- Utilized advanced computational techniques to analyze discrepancies in experimental binding affinities and assess therapeutic potential.
Conclusions:
- Antibody therapies are crucial for combating COVID-19.
- Structural and computational analyses provide insights into antibody efficacy against SARS-CoV-2.
- Further investigation into antibody-antigen interactions is vital for developing effective COVID-19 treatments.
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