Research Highlight: Olvera de la Cruz
Enhanced Binding of SARS-CoV-2 Spike Protein to Receptor by Distal Polybasic Cleavage Sites
Monica Olvera de la Cruz and Baofu Qiao found a new vulnerability in SARS-CoV-2, which could potentially be a target for therapeutic design for COVID-19. The polybasic cleavage site on SARS-CoV-2 is unique, and has not been found on its close relative SARS-CoV (2003) and other similar coronavirus. By means of computer simulations at atomistic and coarse-grained levels, the team found that the polybasic cleavage site can elevate the viral spike protein binding to the human cell receptor. This is surprising since the polybasic cleavage sites are distributed around 10 nanometer from the human cell receptor. “We didn’t expect to see electrostatic interactions at 10 nanometers,” Qiao said. “In physiological conditions, all electrostatic interactions no longer occur at distances longer than 1 nanometer.”
To neutralize the oppositely charged polybasic cleavage site, the team designed a negatively charged tetrapeptide, which remarkably destabilized the viral protein binding to the human cell receptor by around 30%. “Our work indicates that blocking this cleavage site may act as a viable prophylactic treatment that decreases the virus’ ability to infect humans,” said Olvera de la Cruz.
The paper was published in the journal ACS Nano.
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