A new peer-reviewed study University of Colorado Anschutz Medical Campus (USA) offered answers on why delta is the deadliest variant of SARS-CoV-2.
Since June, the number of Covid-19 infections has started to rise again, as the omicron variant began to pick up mutations in the delta variant that gave rise to the new BA.4/BA.5 subvariants. Of the five known variants that have been shown to evade therapeutic antibodies and vaccines developed against the original wild-type SARS-CoV-2 virus, the delta variant is the most virulent and the most causes severe symptoms and increased mortality among those infected.
In their work, published in the scientific journal “Journal of Molecular Biology”, the researchers carried out robust biophysical analyzes of the delta variant and the individual mutations that make it up.
“Our results help to explain why patients who have been vaccinated are still able to be infected with the new variants and why patients who have contracted the delta variant are more likely to be hospitalized,” explains one of the authors. works, Krishna Mallela.
Researchers have identified the effect of mutated residues in the receptor binding domain (RBD) through which SARS-CoV-2 binds to ACE2 receptors that decrease the neutralizing capacity of antibodies approved drugs and polyclonal plasma from cured patients.
“Because we know that vaccines are becoming less and less effective against emerging SARS-CoV-2 variants, it is important to understand which mutations are driving this decrease in neutralization capacity,” Mallela explains.
Scientists present crucial information about mutated residues that now appear frequently in SARS-CoV-2 variants.
“Since we performed individual analyzes of these mutations, we have a fundamental understanding of how some residues affect immune evasion and the infectivity of SARS-CoV-2,” Mallela comments.
The researchers found that delta exhibited unique biophysical characteristics, unlike earlier alpha, beta, and gamma variants. The human immune system generates antibodies to neutralize the virus in response to infection.
These neutralizing antibodies have been classified into different classes, based on the location of their epitope on the RBD, and some of these antibodies have already been approved for emergency use.
Results from Mallela’s lab indicated that the delta variant evolved to evade antibodies classes 2 and 3, instead of enhancing receptor binding or evading class 1 antibodies.
Class 1 antibodies bind the RBD only in the upstream conformation, in which the RBD is accessible to ACE2 binding, while class 2 and 3 antibodies bind the RBD whether it is in the upstream conformation (accessible to ACE2) or descending conformation (inaccessible to ACE2). Delta also shows increased expression of the protein.
One of the delta variant mutations, T478K, is thought to have evolved from patients infected with earlier variants of SARS-CoV-2. This mutation has been shown to evade antibodies generated by previous Covid-19 infections.