Researchers from Argentina and Germany were able to describe an evolutionary mechanism of Molecular aging”Which could play a key role in the evolution and emergence of new variants of the coronavirus, and would allow the development of innovative therapies to combat SARS-CoV-2.
Through bioinformatic-evolutionary, biochemical and mathematical modeling studies, scientists were able to describe this mechanism that takes place at different sites in a region of the Spike protein called RBD, which is the one that binds to hACE2 receptors on human cells to initiate infection.
The study of this protein is key since it is the main target of neutralizing antibodies that block infection, produced by the immune system upon infection with the virus or inoculation with currently available vaccines.
Scheme of the new coronavirus SARS-CoV-2. The scientists were able to describe changes that occur at the molecular level in the Spike proteins located on the surface of the pathogen.
According to the results published in the “Journal of Biological Chemistry”, the researchers identified that the fragment of the Spike protein that establishes direct contact with the hACE2 receiver is particularly enriched at sites that contain the amino acid asparagine and that are altered by chemical modification spontaneous called “deamidation.”
“This reaction occurs within hours to days and changes the ability of Spike to bind to the receptor,” explained Leonardo Alonso, leader of the advance and researcher at the Institute of Nanobiotechnology (NANOBIOTEC), which depends on CONICET and the UBA.
“If molecular aging in these regions of the protein reduces the infectivity of the virus, one would think that if that site is not beneficial it should disappear during evolution. But if it is maintained over time in ‘generations’ of viruses it is because an advantage they give the pathogen in terms of survival and replication, “said Alonso.
The scientist added that those sites of the Spike protein could perhaps mediate other relevant functions, such as deploying strategies to evade the immune system.
“In the last year and a half, we have all witnessed how the new SARS-CoV-2 coronavirus gave rise to new variants with a greater infectivity,” said Sebastián Klinke, also an author of the study and a CONICET researcher at the Leloir Institute. . And he added that molecular aging “could have key implications for understanding viral infection and vaccine development”.