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

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 In fact, many commercial antibodies that received Emergency Use Authorization from the FDA had their status rescinded because they fail to work against newer variants.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.

商业抗体针对SARS-CoV-2刺突蛋白已被成功应用于治疗COVID-19患者。遗憾的是，随着SARS-CoV-2病毒的演变，新的变种出现，能够逃避部分这些抗体。实际上，许多获得美国食品药品监督管理局（FDA）紧急使用授权的商业抗体因无法对抗新变种而撤销其授权。本项目为学生提供了探究不同商业抗体对SARS-CoV-2变种作用效果的机会。在主要研究环节中，学生利用NextStrain.org网站定位SARS-CoV-2的新兴变种，并在GenBank中查找其刺突蛋白的序列。他们运用iCn3D和BLAST工具将变种刺突蛋白的序列与商业抗体结合的刺突蛋白序列进行比对。他们对变种刺突蛋白的抗体结合位点进行注释和识别突变。最后，他们比较原始氨基酸与抗体之间形成的化学键，以及预测的变种氨基酸可能形成的键，以预测其抗体对变种的有效性。