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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): Sandra Porter1, Uwe Hilgert2, Erica Lannan3, Michelle Stieber4

1. Digital World Biology 2. Bio5 Institute 3. Prairie State College 4. Cerritos College

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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 In fact, many commercial antibodies that received Emergency Use Authorization from the FDA had their status rescinded because they fail to work against newer variants.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 1.0 - published on 10 Jun 2022 doi:10.25334/82D0-AT65 - cite this

Description

This resource contains the following items:

1.  A spreadsheet with information for molecular structure models for ten different commercial antibodies. One of these antibodies is used as an example in the video and the instructions. Each structure is accompanied by the PDB ID, the name of antibody, the name of the drug, and notes about it's effectiveness against different variants.

2.  A spreadsheet with information from the CDC about the effectiveness of different antibodies against different variants as of May 3, 2022.

3.  An Instructor guide that describes all the parts of the activity and discusses how an instructor would assign different antibodies to students and have them carry out the research project.

4.  A Student guide describing different parts of the activity.

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 sheet 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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