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Evaluating the potential for immune escape: how likely is an antibody to protect against a specific SARS-CoV-2 variant?

Author(s): Allyson Sterling1, Erica Lannan2, Sandra Porter3

1. Regis University 2. Prairie State College 3. Digital World Biology

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Antibody Engineering

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Summary:
Commercial antibodies to the SARS-CoV-2 spike protein have been successfully used to treat people with COVID-19. Unfortunately, as the SARS-CoV-2 virus evolves, new variants have appeared that can escape some of these antibodies. In fact, many…

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Commercial antibodies to the SARS-CoV-2 spike protein have been successfully used to treat people with COVID-19. Unfortunately, as the SARS-CoV-2 virus evolves, new variants have appeared that can escape some of these antibodies. In fact, many commercial antibodies that received Emergency Use Authorization from the FDA had their status rescinded because they fail to work against newer variants. This project gives students the opportunity to investigate how well different commercial antibodies might work against SARS-CoV-2 variants. In the main research component, students use NextStrain.org to locate emerging variants of SARS-CoV-2 and find the sequences of their spike proteins in GenBank. They use iCn3D and BLAST to align the sequence of the variant spike protein to a sequence of a spike protein that is bound to a commercial antibody. They annotate and identify mutations in the antibody binding site of the variant spike protein. Last, they compare the chemical bonds that would be formed between the original amino acid and the antibody with the predicted bonds that could be formed by the variant amino acid and predict whether their antibody will be effective against their variant.

Licensed under CC Attribution-NonCommercial 4.0 International according to these terms

Version 2.0 - published on 24 May 2024 doi:10.25334/Q7KG-5V20 - cite this

Adapted from: Evaluating the potential for immune escape: how likely is an antibody to protect against a specific SARS-CoV-2 variant? v 1.0

Keywords

  1. course based undergraduate research experiences
  2. BLAST
  3. molecular modeling
  4. SARS-CoV-2
  5. antibody
  6. Nextstrain
  7. iCn3D
  8. Sequence alignment
  9. Structure alignment

Alignments

  1. Resource Type
  2. Audience Level
  3. Activity Length
  4. Software Used
  5. Open Science and Education Practices Ontology
Contents:
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Description

This resource updates the 2022 version with new workflows from iCn3D  and contains the following items:

1. An Instructor resource describing some tips for using this resource with students, including changing the pathogen of interest.

2.  A Student guide describing different parts of the activity, including a worksheet and answer key.

There are five parts to the activity. The first three are optional and last two parts are the main research project. The optional parts (1, 2, and 3) describe how students can compare conformations of the spike protein receptor binding domain (part 1), find aligned models from different structures (part 2), and identify a protein binding site (part 3).

The research component consists of finding a protein sequence from a variant (part 4) and comparing that sequence to an older version of the spike protein to evaluate how mutations may impact antibody binding (part 5).

Each part is accompanied by a worksheet for recording experimental data.  The data sheets also make it easier for an instructor to assess the quality of the work because students have some guidance concerning the type of information that needs to recorded.

Lastly, a PowerPoint presentation is provided that goes through the research project and a video that illustrates the technical components.

This work was funded by the National Science Foundation under Grant No. (DUE 2055036). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

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