Researchers at Northwestern University (United States) have discovered a new vulnerability in the spike protein of the new coronavirus, advancing a relatively simple potential treatment pathway.

The spike protein contains the virus binding site, which attaches itself to host cells and allows the virus to enter and infect the body. Using nanometer-level simulations, the researchers discovered a positively charged site (known as the polybasic cleavage site) located 10 nanometers from the actual binding site of the spike protein. The positively charged site allows a strong binding between the virus protein and negatively charged human cell receptors.

Taking advantage of this discovery, the researchers engineered a negatively charged molecule to bind to the positively charged cleavage site. Blocking this site inhibits the binding of the virus to the host cell.

« Our work indicates that blocking this cleavage site may act as a viable prophylactic treatment that decreases the ability of the virus to infect humans. Our results explain experimental studies showing that mutations in the SARS-CoV spike protein- 2 affected the transmissibility of the virus « , explains Mónica Olvera de la Cruz, leader of the research, which has been published in the magazine ‘ACS Nano’.

Made up of amino acids, SARS-CoV-2 polybasic cleavage sites have remained elusive since the COVID-19 outbreak began. But previous research indicates that these mysterious sites are essential for virulence and transmission. The researchers found that the polybasic division site is located 10 nanometers from human cell receptors, a finding that provided unexpected insight. « We did not expect to see electrostatic interactions at 10 nanometers. Under physiological conditions, all electrostatic interactions no longer occur at distances greater than 1 nanometer, » they point out.

« The function of the polybasic cleavage site has remained elusive. However, it appears to be cleaved by an enzyme (furin) that is abundant in the lungs, suggesting that the cleavage site is crucial for virus entry into human cells. » , adds Olvera de la Cruz.