New studies have revealed an unprecedented mechanism behind the loss of neutralizing antibodies against the alarming pandemic coronavirus.
The study shows that three mutations in the Corona virus spike protein in the Epsilon variant inhibit the effectiveness of antibodies caused by current vaccines or previous Corona virus infections.
Mutations give this type of worrying coronavirus a way to completely evade the monoclonal antibodies used in clinics and reduce the effectiveness of the antibodies from the plasma of vaccinated people.
To better understand immune escape strategies, scientists have visualized the infection mechanism of this variant to see what is different from the original composition of the pandemic coronavirus, and what are the implications of these changes.
The international project was led by David Wessler’s lab in the Department of Biochemistry at the University of Washington in Seattle, and Luca Piccoli and David Corti of the Vir Biotechnology Foundation.
The Fissler laboratory and his collaborators have been exploring, for several years, the molecular morphology and infection mechanisms of SARS-like coronaviruses, and also examining how antibodies try to block infection mechanisms, and how variants find new quirks.
Their latest data shows that the epsilon variant “relies on an indirect and unfamiliar strategy of neutralization and escape.”
Molecular clock analysis determined the timing of the appearance of precursors for the epsilon variant in May 2020 in California. By the summer of 2020, it had diverged into its B.1.427/B.1.429 subspecies. The cases of “Covid-19” from the variant increased rapidly, and the variant quickly spread in the United States. It has now been reported in at least 34 other countries.
To learn more about the properties of the epsilon variant, the researchers tested the resilience against the epsilon variant from plasma from people exposed to the virus, as well as people who had been vaccinated. The plasma neutralization efficacy against the epsilon variant of concern was reduced by 2- to 3.5-fold.
Like the original SARS-CoV-2, the variant infects target cells through the glycoprotein spike, the structure that crowns the surface of the virus.
The researchers found that epsilon mutations were responsible for rearranging critical regions of the spike protein. Microscopic studies showed structural changes in these areas.
Visualizing these mutations helps explain why it is so difficult for antibodies to bind to the glycoprotein spike.
One of the three mutations in the epsilon variant affected the receptor-binding domain of the spike protein. This mutation reduced the neutralizing activity of 14 of the 34 domain-specific neutralizing antibodies, including those in the clinical phase, according to rt.
The other two of the three mutations in the variant affected the N-terminal domain of the spike protein.
The researchers used mass spectrometry and structural analysis to find that part of the coronavirus’s peripheral domain was reshaped by these mutations.
