“The firing zone is barely two meters in diameter… A hit will trigger a chain reaction that will blow up the Death Star“, said the rebel officer Jan Dodonna while explaining to his troops how to reach the weak point of the terrifying combat station of the first part of Star Wars. A tiny area compared to the gigantic size of the famous “Dark Star”. Just like the weak point that researchers have just found in the coronavirus responsible for Covid-19. Except that here the firing zone is less than a nanometer! But, according to an article published on August 18, 2022 in NatureCommunications, it could allow us to neutralize any variant of the coronavirus, no matter how many mutations it tries to hide with.
A weak point that mutates very little
This flaw in the coronavirus is in the Spike protein, in the domain that hooks onto the ACE2 receptor in human cells (called RBD) and allows it to infect us. This area is made up of barely a dozen amino acids (while the Spike protein has a total of 1,273 amino acids). Precisely the few amino acids that are found in direct contact with ACE2. Researchers from the University of British Columbia (Canada) described this region, showing that it mutates very little, probably because any major change would decrease affinity with the ACE2 receptor. So this zone only accepts small modifications that do not change the structure of the zone, so that the receiver is still recognized and hooked up as well.
Because of this constraint, this area has remained almost unchanged in all variants of the coronavirus that have emerged since the start of the pandemic. Only two frequent substitutions are listed there: L452R (found in the Delta variant and the Omicron sub-variants BA.4 and BA.5) and Q493R (present in certain Omicron sub-variants). “The epitope (part of a molecule capable of stimulating the production of an antibody, editor’s note) that we describe in this article is far from the majority of the mutational “hot spots” of the virus, which is why these characteristics are preserved in all the variantssummarizes Sriram Subramaniam, researcher at the University of British Columbia and author of the study, in a communicated. The description of this structure in detail opens up a whole field of possible treatments.”
An antibody succeeds in blocking this site
And the researchers don’t just describe this weak point of the coronavirus to us, they also reveal the weapon that we could use to reach it! A piece of antibody that manages to cling to it and thus prevents the virus from recognizing the ACE2 receptor. This is a domain VH, the variable region of the heavy chain (“heavy” in English, hence the H) of an antibody. This VHnamed Ab6, was artificially designed by researchers at the University of Pittsburgh (USA) in June 2020. It has the particularity of recognizing this region of the Spike and of accessing it with a precise angle (almost perpendicular to the RBD domain of Spike) to stick to it as well as possible and thus drive out the ACE2 receptor.
This piece of antibody thus manages to recognize all the major variants of the coronavirus, Delta and Omicron included, even if its neutralization capacity is however reduced in the face of these variants because of the L452R and Q493R mutations. “We now know all the interactions that the Spike protein has with this antibody in this site. With this information we can design a whole slew of variant-resistant antibodies, which would completely change our fight against Covid-19.“, continues Sriram Subramaniam. It remains to be verified whether this piece of antibody retains its effectiveness. live and if he will be able to bring us our Luke Skywalker against the coronavirus.