Like the rebel alliance that inflates the thermal exits of the Death Star as the legendary Greek warrior Achilles is the victim of nothing more than an arrow lying in his ankle, seemingly unstoppable forces often inflict a small weakness that subdues them proves.
Now, Northwestern University researchers have discovered a new vulnerability within SARS-CoV-2’s genetic structure that may just prove to be the Achilles heel of the coronavirus. The authors of the study say that this revelation paves the way for a new, simpler approach to treating coronavirus.
More specifically, this discovery applies to the coronavirus’ spike protein.
Although the word protein is synonymous with dumbbells and biceps, in this case SARS-CoV-2’s spike protein is essentially what gives the virus its nasty ability to infect new people so quickly. The spike protein contains the virus’ binding page that is what attaches itself to new host cells, allowing the coronavirus to enter and infect host after host.
All of this is not groundbreaking news for scientists, but here’s where things get interesting. Through a series of nanometer-level simulations, the team at Northwestern noticed a positively charged area located just 10 nanometers from the binding site of the spike protein.
This positively charged area, referred to as the polyphasic cleavage site, appears to function as a helper of sorts in the bonding process to a new host. The positive charge of polybasic cleavage supports a stronger link between the protein-picking coronavirus and the negative charge of human cell receptors.
However, in making this discovery, the research team soon realized that they might be able to take advantage of the polybasic cleavage site. That said, they designed and created a custom negative charge molecule that would bind to the positively charged polybasic cleavage site just like a human cell.
The idea here is that if the coronavirus binds itself to this decoy, it will not be able (or at least less able) to actually infect new people and spread them further.
“Our work suggests that blocking this cleavage site may act as a viable prophylactic treatment that reduces the virus’ ability to infect humans,” said study leader Monica Olvera de la Cruz, attorney Taylor Professor of Materials Science and Engineering at the McCormick School of Northwestern Engineering, in a publication. “Our results explain experimental studies showing that mutations in the SARS-CoV-2 spike protein affect the transmissibility of the virus.”
Polybasic splitting sites are not a completely new concept. Preliminary studies conducted long before COVID-19 had suggested that these viral regions, consisting of amino acids, are important components of the spread and transmission of viruses in general. For some reason, however, the localization of SARS-CoV-2’s polybasic cleavage site was evident until this study was difficult.
“The function of the polybasic cleavage site has remained incomprehensible,” adds Professor Olvera de la Cruz. “However, it appears to be cleaved by an enzyme (furin) that is abundant in the lungs, suggesting that the cleavage site is crucial for the introduction of viruses into human cells.”
“We did not expect electrostatic interactions to be seen at 10 nanometers,” commented first study author Baofu Qiao, a research assistant in the Olvera de la Cruz research group. “In physiological conditions, all electrostatic interactions no longer occur at distances longer than 1 nanometer.”
The research team is already planning to work with both chemists and pharmacologists at Northwestern to begin developing a new drug that incorporates these findings.
The full study can be found here, published in ACS Nano.
