Researchers are developing rapid methods to identify antibody-resistant SARS-CoV-2 mutants

Researchers in the United States are explaining a new and rapid method for identifying antibody-resistant variants of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2).

SARS-CoV-2 is the root cause of the global pandemic of coronavirus disease 2019 (COVID-19), first identified in Wuhan, China in December 2019. To be more contagious or to avoid neutralization from antibodies.

These escape mutations are a major concern as antibody-resistant virus strains can be dramatically reduced. Effectiveness of Current vaccine and antibody therapies.

Currently, a team of scientists at the University of Colorado and other institutions are reporting yeast screening methods that can be used to quickly identify escaped variants. Neutralizing antibody (NAbs).

We have identified five nAb escape mutants, including three from the official germline class VHC-53 induced by natural COVID-19 infection, “the authors say. “We provide libraries, methods, and software as openly available community resources to accelerate new therapeutic strategies for SARS-CoV-2.”

The preprinted version of the research treatise can be read completely at bioRxiv*server.

What did the researchers do?

Understanding the role and function of SARS-CoV-2 mutations plays a major role in the development of adequate vaccines, boosters, and antibody therapies. The only viral membrane protein involved in cell invasion is the spike (S) protein, which binds to the host via the receptor binding domain (RBD). Researchers wanted to develop a functional screening assay that could identify nAb escape mutants on a large scale.

The S RBD Yeast Surface Display (YSD) platform was created and tested to measure and predict the escape potential of RBD. After testing with a panel of 11 anti-SRDB antibodies, we were able to conclude that the yeast platform was able to “faithfully” emulate the binding interactions between neutralizing antibodies and SRBD.

Next, researchers sought to identify SRBD escape mutants using five nAbs that were able to block ACE2 binding from SARS-CoV-2. They identified 97 SRBD mutations in the SARS-CoV-2 pseudovirus that could escape recognition by at least one neutralizing antibody. Primarily, the mutants F486I, E484K, T478R, K417N, K417T, and D420K were able to completely avoid neutralization from common antibodies, consistent with previous studies, to many of the variants of concern. We confirmed that the existing N501Y mutation does not play a role in providing antibody resistance. Instead, it may increase the binding affinity for ACE2.

These findings were awarded using biological replication of the SARS-CoV-2 mutant from the public library and confirmed that the escape mutant had a lower resistance to antibody than the other mutants.

What does this mean?

The authors report some of the key benefits of yeast-based screening methods. In short, this method can accurately mimic viral infections and antibody binding, but provides a safer working environment, with relatively fast identification of escaped mutants and “robust and rigorous” identification of these mutants. Provides an algorithm.

The team will identify this new yeast screening method as a publicly available community resource to help scientists accelerate the development of therapeutic strategies for SARS-CoV-2, and to identify specific nAb-resistant mutations. Presented as a new tool for.

Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.