Epsilon variant mutations contribute to COVID immune evasion

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Three mutations in the Epsilon coronavirus peak protein dampen the neutralizing potency of antibodies induced by current vaccines or past COVID infections.

Mutations give this variant of coronavirus concern a means to completely elude the specific monoclonal antibodies used in clinics and reduce the efficacy of plasma antibodies in vaccinated individuals.

To better understand the exact immune escape strategies working here, the scientists visualized the infection machinery of this variant to see what is different from the original pandemic coronavirus configuration and what the implications of these changes are.

The international project was led by David Veesler’s lab in the Department of Biochemistry at the University of Washington in Seattle and by Luca Piccoli and Davide Corti of Vir Biotechnology.

For several years, the Veesler Laboratory and its collaborators have been exploring the molecular conformation and infection mechanics of SARS-like coronaviruses. They also examine how antibodies try to block the mechanisms of infection and how variants present new dodges.

Their latest data show that the Epsilon variant “depends on an indirect and unusual neutralization-escape strategy,” according to the researchers.

His findings are published as a First Release article in Science.

A molecular clock analysis timed the onset of the Epsilon variant precursor until May 2020 in California. The summer of 2020 had diverged in its B.1.427 / B.1.429 lineages. COVID cases of the variant increased rapidly and the variant soon spread to the United States. It has now been reported in at least 34 more countries.

To learn more about the characteristics of the Epsilon variant, the researchers tested the resistance to the plasma Epsilon variant of people who had been exposed to the virus, as well as vaccinated people. The neutralizing power of plasma against the worrisome variant of Epsilon was reduced approximately 2 to 3.5-fold.

Like the original SARS-CoV-2, the variant infects target cells through its spike glycoprotein, the structure that crowns the surface of the virus. The researchers found that Epsilon mutations were responsible for rearrangements in critical areas of ear glycoprotein; electron cryomicroscopy studies showed structural changes in these areas.

Visualization of these mutations helps explain why antibodies had difficulty binding to spike glycoprotein.

One of the three mutations in the Epsilon variant affected the spike glycoprotein receptor binding domain. This mutation reduced neutralizing activity 14 of 34 domain-specific neutralizing antibodies, including antibodies in the clinical phase.

The other two of the three mutations in the variant affected the N-terminal domain of the ear glycoprotein. The researchers used and structural analysis to find that part of the coronavirus N-terminal domain was remodeled by these .

The cleavage site of the signal peptide was changed to the NTD antigenic supersite and a new disulfide bond formed. This resulted in a total loss of neutralization by 10 out of 10 tested specific for the N-terminal domain in the ear glycoprotein.

The scientist believed that the discovery of immune evasion mechanisms, such as this new mechanism based on signal peptide modification, is as important as variant surveillance by RNA sequencing. Together, they point out, these efforts could help successfully combat the ongoing pandemic.


Structural changes in the alpha and beta variants of SARS-CoV-2 were identified


More information:
Matthew McCallum et al, SARS-CoV-2 immune evasion by variant of concern B.1.427 / B.1.429, Science (2021). DOI: 10.1126 / science.abi7994

Citation: Epsilon variant mutations contribute to COVID immune evasion (2021, July 6) recovered on July 6, 2021 at https://medicalxpress.com/news/2021-07-epsilon-variant-mutations- contribute-covid.html

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