Scientists Discover Opportunity To Disrupt SARS-CoV-2 Dynamics, Prevent COVID-19 Transmission

Spike protein as the virus fuses with host human cells reveals an opportunity to disrupt dynamics and halt transmission.

Scientists have simulated the transition of the SARS-CoV-2 spike protein structure from when it recognizes the host cell to when it gains entry, according to a study published on August 31, 2021, in eLife.

The research shows that a structure enabled by sugar molecules on the spike protein could be essential for cell entry and that disrupting this structure could be a strategy to halt virus transmission.

To infect a human cell, the S1 subunit binds to a molecule on the surface of human cells called ACE2, and the S2 subunit detaches and fuses the viral and human cell membranes.

The simulations revealed that glycans form a 'cage' that traps the 'head' of the S2 subunit causing it to pause in an intermediate form between when it detaches from the S1 subunit and when the viral and cell membranes are fused.

"Our simulations indicate that glycans can induce a pause during the spike protein transition. This provides a critical opportunity for the fusion peptides to capture the host cell," concludes co-author Paul C. Whitford, Associate Professor at the Center for Theoretical Biological Physics and Department of Physics, Northeastern University, Boston, US. "In the absence of glycans, the viral particle would likely fail to enter the host. Our study reveals how sugars can control infectivity, and it provides a foundation for experimentally investigating factors that influence the dynamics of this pervasive and deadly pathogen."

Reference: "Sterically confined rearrangements of SARS-CoV-2 Spike protein control cell invasion" by Esteban Dodero-Rojas, Jose N Onuchic and Paul Charles Whitford, 31 August 2021, eLife.
 

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