Wednesday, May 29

Why is SARS-CoV-2 so contagious? 2023

JMU researchers have shown why SARS-CoV-2 coronavirus spread so efficiently must be rethought.

Why the COVID-19 epidemic spread so quickly is unknown. As previously thought, the virus does not spread swiftly by attaching with numerous surface proteins simultaneously to several receptors of the cell to be infected or to a single receptor leading to the docking of more receptors.

Simone Backes, Gerti Beliu, and Prof. Markus Sauer have shown that a single virus attaches to a single receptor, enabling very effective infection.

SARS-CoV-2’s 20–40 spike proteins interact to ACE2 receptors. Antibodies inhibit these receptors, preventing infection. “This suggests that the binding of the virus to the ACE2 receptor is the decisive step in infection,” Sauer says.

Monitoring ACE2 receptors and their interaction with viral spike proteins is difficult, thus much was left to speculation—such as whether viruses attach to many receptors with several spikes to enter the cell.

Another suggestion was that membrane receptors in pairs or groups of three bind more efficiently to trimeric spike proteins, or that they only form such groups after attaching to a spike protein. Both depend heavily on membrane ACE2 receptor density.

Würzburg researchers dyed antibodies to count receptors and better comprehend these theories. Markus Sauer’s single-molecule sensitive super-resolution microscopy technology dSTORM and SARS-CoV model cell lines were utilized in the investigation.

Exploring coronavirus cell entrance.

The scientists found that the average distance between nearby ACE2 receptors is 500 nanometers, substantially bigger than a virus particle (100 nanometers). Thus, a viral particle with numerous spike proteins cannot concurrently connect to various receptors.

The membrane receptors are not in pairs or threes. They occur alone there. “Even after a viral spike protein binds to them,” Beliu explains. If a spike attaches to a receptor, an infection occurs.

These data disproved numerous viral particle-multiple ACE2 receptor ideas. As predicted, host cells with increased ACE2 expression facilitate SARS-CoV-2 infection.

To learn more about coronavirus cell entrance, Würzburg researchers aim to utilize high-resolution light sheet microscopy. This may improve COVID-19 prevention and medication development.

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