Viral S proteins interact with a cellular receptor to allow SARS-CoV-2 to enter our cells. However, researchers in the United States have shed light on an area of this hopeful protein. By modifying it, it would be possible to reduce the intensity of interactions.
Act on another area of the S protein
Since the appearance of the SARS-CoV-2 coronavirus, the S (surface) protein is certainly the most studied element of its structure. This protein binds to the angiotensin-converting enzyme 2 (ACE2), a receptor that allows coronavirus to enter a host cell. However, the S protein contains a particular zone, the Receptor binding site (RBD). This corresponds to the end of the protein directly in contact with the ACE2 receptor.
In a study published in the journal ACS Nano on August 2, 2020, researchers from Northwestern University (United States) say they have identified another interesting area of the S protein. This is very close to the RBD area (10 nanometers ). According to the study leaders, if this new area is changed, the RBD-ACE2 link could be weakened.
The researchers suggest a polybasic cleavage site, composed of three arginines and an alanine, giving it an overall positive charge for an enzyme called “furin”. However, this cut is necessary for the activation of the fusion of the viral envelope with the membrane of the host cell. Thus, the scientists carried out a comparison between the RBD-ACE2 bond concerning the basic protein S with two mutants whose polybasic cleavage was modified. In the case of the first mutant, the scientists removed the amino acids from the polybasic site. For the second, it is a question of replacing two of these amino acids.
The results show a reduction in RBD-ACE2 interactions of 36% for the first mutant and 20% for the second. This made it possible to understand that modifying part of the S protein other than RBD also influences the ability of the protein to infect our cells! Given the quality of the results obtained by the researchers, they believe that this polybasic site should be targeted therapeutically. Scientists have synthesized a small peptide made up of four negatively charged amino acids. The results are promising as we are talking about a 41% reduction in hydrogen bonds. Thus, this lays the basis for a treatment weakening the RBD-ACE2 link.
However, it should be noted that for the moment, this research remains theoretical. Indeed, no test has been performed in vitro. Researchers are only at the stage of assuming that weakening interactions between RBD and ACE2 may lessen the infectivity of the coronavirus.