Each of the three approved Qur’anic Vaccine Vaccines 2019 (COVID-19) – Moderna, BioNTech-Pfizer and Oxford-Astrazeneca – generate the protein spike forms of severe coronavirus 2 (SARS-CoV-2), allowing immune system to respond with the appropriate antibodies. Since viruses are able to adapt and mutate at high rates, such vaccine loads may eventually become ineffective and so locating highly conserved regions of the protein would be useful in developing additional therapies.
A recent study by scientist Robert Penner at the Institut des Hautes udestudes Scientifiques in France uses free energy calculations to predict effective targets against highly conserved, surface-accessible, interactive and mutant-resistant viruses. The study is available at bioRxiv* server.
What is energy without backbone protein?
Free backbone (BFE) is a measure of the freedom of a part of a protein structure, which depends mainly on the number of hydrogen bonds between the regions. Therefore, regions with high BFE are more likely to undergo greater modulatory change at some point, for example, while the peak virus protein penetrates and fuses with the host cell.
Protein geometry is the main way in which immune cells recognize a pathogen and independent proteins can take on a different configuration than when part of a larger macromolecule. Therefore, vaccine loads must reproduce on the spot configure the live virus as close as possible to elicit the ideal response.
High BFE is only maintained evolutionarily if necessary for a particular function. In cases where many types of coronaviruses persist, function must be critical for the virus to multiply and survive. Unfortunately, the highly structured mobility of these regions reduces their attractiveness as viral targets, as targeting the changing three-dimensional structure becomes more difficult. Low BFE sites, in contrast, are more static in configuration and are likely to fold similarly individually. In addition, as low BFE sites are surrounded by a large number of hydrogen bonds, any mutations at the BFE site should retain the antigen structure. Any mutations here will not be critical for them to function and will thus be adopted on a large scale by evolutionary pressures.
How can low BFE sites be used?
Therefore, highly conserved low BFE sites are relatively rare. Since they are retained in many strains of the Koran, they must play an essential function, although they are static and therefore serve a good, stable target of drugs. The researcher hypothesizes that immobilizing passive low BFE sites may affect the activity of nearby high BFE sites that are critical to operation.
Several variants of SARS-CoV-2 concern have been identified with mutations in the pin protein that allow modification changes beyond those observed in the wild. The greater freedom of configuration is implied to be involved in the greater transmissibility seen in these strains. The team received 29 structural records for SARS-CoV-2 spike proteins from various variants of concern. Mutant residues were identified and BFE was compared, with about half of the mutants exhibiting higher BFE than wild-type counterparts due to fewer hydrogen bonding interactions.
The functional purpose of certain residues can be deduced from their modulatory changes at a specific pH. For example, a mutant residue was observed to have high BFE at low pH, indicating the need for greater modulatory activity in more acidic environments, such as when entering cells via the intracellular pathway.
Four passive sites of interest of nine base pairs were identified that were accessible to the surface of the SARS-CoV-2 spike protein common to each of the 29 variants of concern, each with low BFE and each located upstream of a large active binding supernatant. These sites could play a role in the critical functioning of the SARS-CoV-2 spike protein, and exploitation of these sites could play a future role in the development of reliable and long-lasting COVID-19 vaccines.
BioRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be construed as convincing, guiding clinical practice / health-related behavior or treated as standard information.