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New research reveals why COVID-19 antibody treatment is not so effective against new mutants

BiochemistryCover. Convergent evolution of multiple mutations increases the fitness of the SARS-CoV-2 virus by balancing positive and negative choices, together improving the likelihood of mutation choices. credit:Biochemistry“width =” 800 “height =” 530 “/>

Cover Biochemistry.. Convergent evolution of multiple mutations increases the fitness of the SARS-CoV-2 virus by balancing positive and negative choices, together improving the likelihood of mutation choices. credit: Biochemistry

New research published in today’s issue Biochemistry Is the first person to investigate the effects of multiple mutations on the evolution of SARS-CoV-2 mutants. The findings will help scientists better understand the characteristics of current and new variants.

This result can also be used to better inform the development of vaccines and treatments to counter the threat posed by variants.

“Early studies, including us, focused on explaining a single effect. mutation It is not the underlying mechanism of mutation co-evolution. ” Pharmaceutical science At the University of Colorado Skaggs Faculty of Pharmacy and Faculty of Pharmacy on the University of Colorado Anschutz Medical Campus.

“Our research helps explain the concept of convergent evolution by balancing positive and negative evolutionary pressures,” he adds.

The cover of the journal features a new newspaper co-authored by Alexandra Lucas from Vaibhav Upadhyay, Casey Patrick and Mallela’s lab. This paper provides a physical basis for why approved antibody therapies do not help neutralize recent variant of concern variants such as Omicron and its subvariants.

“Understanding the underlying mechanisms of antibody escape and the location of peplomer mutations can be achieved by targeting epitopes with minimal mutations or by developing a wide range of neutralizing antibodies that target multiple epitopes. , Helps develop new antibody therapies that work against new mutants, “says Marella.

This study found that specific mutations recur in new mutants that exhibit convergent evolution. One such evolution occurs at the three amino acid positions K417, E484, and N501 in the receptor binding domain (RBD) of peplomer proteins. Almost half of the 4.3 million variant sequences in the GISAID database containing any of these three mutations have all three occurring simultaneously. Individual mutations have both beneficial and harmful / harmful effects, but when they are combined, the harmful / harmful effects are canceled and the choice of mutation is improved.

Researchers Convergent evolution Analysis of three mutations by describing the individual and collective effects of the mutation on binding to the angiotensin converting enzyme 2 receptor, antigenic escape from neutralizing antibodies, and protein stability and expression.

They found that the three RBD mutations played a very clear and specific role, improving viral compatibility and contributing to building their case. Positive selection, Even though individual mutations have the detrimental effect of making them a negative choice. Compared to wild-type, K417T avoids class 1 antibodies and has improved stability and expression. However, ACE2 receptor binding is reduced. E484K avoids class 2 antibodies. However, receptor binding, stability, and expression are reduced. N501Y increases receptor binding. However, it is less stable and less expressive. When these mutations come together, Harmful effects It is mitigated by the presence of compensatory effects. The triple mutant K417T / E484K / N501Y increases ACE2 receptor binding, evades both class 1 and class 2 antibodies, and exhibits stability and expression similar to wild type.

The authors conclude that the collective effect of these mutations is far more favorable for viral fitness than individual mutations, and that the presence of multiple mutations improves individual mutation selection. ..

“As SARS-CoV-2 evolves from alpha to omicron, more and more mutations are accumulating. By providing research to understand the role of these mutations, research and new treatments, Marella said. We hope it will help further drive the development of the law. To better fight new variants. ”


How the three mutations work together to spur a new SARS-CoV-2 mutant


Quote: For a new variant (June 7, 2022) obtained from https: //medicalxpress.com/news/2022-06-unravels-covid-antibody-treatments on June 7, 2022 by a new study. Elucidated why COVID-19 antibody treatment is not effective-effective.html

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New research reveals why COVID-19 antibody treatment is not so effective against new mutants

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