Like the rebel alliance that blows up the Death Star’s thermal exhaust or the legendary Greek warrior Achilles who only fell prey to an arrow in his ankle, seemingly unstoppable forces often harbor a tiny weakness that turns out to be their downfall.
Now researchers at Northwestern University have discovered a new vulnerability in the genetic structure of SARS-CoV-2, which may turn out to be the Achilles heel of the coronavirus. The study’s authors say this discovery paves the way for a new, simple approach to coronavirus treatment.
This discovery particularly affects the coronavirus. Spike protein.
While the word protein is synonymous with dumbbell stands and biceps, in this case the SARS-CoV-2 spike protein is essentially what gives the virus its nasty ability to infect new people so quickly. The spike protein harbors the virus̵
None of this is breaking news for scientists, but this is where it gets interesting. Through a series of simulations at the nanometer level, the Northwestern team found a positively charged area just 10 nanometers from where the spike protein was bound.
This positively charged area is called the polybasic cleavage site, seems to act as a kind of helper in the process of binding to a new host. The positive charge of the polybasic cleavage site promotes a stronger connection between the coronavirus spike protein and the negative charge of human cell receptors.
With this discovery, however, the research team quickly realized that it might be able to take advantage of the polybasic cleavage site. So they designed and created a custom negatively charged molecule that binds to the positively charged polybasic cleavage site just like a human cell does.
The idea behind this is that once the coronavirus binds to this bait, it will not be able (or at least less able) to actually infect new people and continue to spread.
“Our work shows that blocking this cleavage site can act as a viable prophylactic treatment that reduces the virus’ ability to infect humans,” says study director Monica Olvera de la Cruz, Attorney Taylor, professor of materials science and engineering at the McCormick School of Northwestern in Northwestern Engineering, in a publication. “Our results explain experimental studies that show that mutations in the SARS-CoV-2 spike protein affect virus transmission.”
Polybasic cleavage sites are not a completely new concept. Previous studies, done long before COVID-19, had shown that these amino acid areas of the virus are important components of the spread and transmission of viruses in general. For some reason, the localization of the polybasic cleavage site of SARS-CoV-2 had proven difficult until this study.
“The function of the polybasic cleavage site is difficult to determine,” 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 critical for virus entry into human cells.”
“We weren’t expecting any electrostatic interactions at 10 nanometers,” comments first study author Baofu Qiao, a research fellow in the Olvera de la Cruz research group. “Under physiological conditions, all electrostatic interactions no longer occur at distances of more than 1 nanometer.”
The research team is already planning to work with chemists and pharmacologists in Northwestern to develop a new drug that takes these findings into account.
The full study can be found here, published in ACS Nano.