A new study has found that COVID-19 antibody treatments are less effective for new variants due to evolving mutations in different strains of virus.
The authors of the study, which was published Tuesday in the peer-reviewed journal Biochemistry, say the findings could be used to better inform the development of vaccines and therapeutics in the fight against emerging coronavirus variants.
University of Colorado Anschutz Medical Campus Professor and Corresponding Author Krishna Mallela says the study can also help scientists understand the properties of current and new variants.
“Previous studies, including ours, have focused on explaining the effect of individual mutations and not the mechanism underlying the coevolution of mutations,” Mallela said in a press release.
“Our study helps explain the concept of convergent evolution by balancing positive and negative selection pressures.”
According to the scientists, the study provides the “physical basis” why currently approved antibody therapies do not work to neutralize recent variants of COVID-19, such as the highly transmissible Omicron variant and its subvariants.
“Understanding the mechanisms underlying antibody release and the location of mutations in the ear protein will help develop new antibody therapies that work against new variants by targeting epitopes with minimal mutations or developing broad neutralizing antibodies that “target multiple epitopes,” Mallela said.
According to the study, the researchers found that certain mutations appear several times in emerging variants that show what is known as convergent evolution.
Scientists point out that one of these evolutions occurs at three amino acid positions: K417, E484, and N501, in the receptor binding domain (RBD) of the COVID-19 ear protein. The study reports that nearly half of the 4.3 million variant sequences in the GISAID database that contain any of these three mutations have all three occurring together.
When individual mutations are joined, the study says that the harmful or adverse effects are reversed, leading to a better selection of the mutations together.
The researchers examined the physical mechanisms underlying the convergent evolution of these three mutations. According to the study, they analyzed the individual and collective effects of these mutations on the binding of antibodies to cell receptors and immune leakage, as well as the stability and expression of proteins.
The study found that all three RBD mutations perform “very different and specific functions” that help them often come together and improve the “viral fitness” of COVID-19 variants: how effectively a virus can pass through. its entire life cycle.
According to the study, K417 was found to escape class 1 antibodies, showing greater stability and expression, but decreased binding capacity.
E484 was found to escape class 2 antibodies, however, the scientists found that it had decreased receptor binding, stability, and expression.
The study said N501Y showed increased receptor binding, but also decreased stability and expression.
When these mutations come together, the scientists found that the harmful effects were mitigated by the presence of “compensatory effects” that correct a loss of viral fitness due to previous mutations.
The study reports that when these three mutations are found together, they show increased receptor binding, escape both class 1 and class 2 antibodies, and exhibit similar stability and expression to the original SARS-CoV-2 strain. . This is why the original virus-targeted strain treatment is less effective.
The study’s authors say the findings suggest that the collective effect of these mutations is “much more beneficial” to the fitness of the virus than individual mutations. They added that the presence of multiple mutations improves the selection of individual mutations.
“As SARS-CoV-2 has evolved from Alpha to Omicron, more and more mutations are accumulating. We hope that by providing research that understands the role of these mutations, we can help further drive research and development. new therapies to better combat new variants, “Mallela said in a statement.