Researchers at Utrecht University (Netherlands) found A complex mechanism that activates the coronavirus spike protein to enter cellsAccording to “Nature” magazine.
The study used powerful microscopy and computer simulations to reveal how tiny sugar molecules bind to the spikes of the human coronavirus and trigger the exposure of components needed to invade host cells, Ep reported.
The findings provide fundamental new insights into the complex mechanisms used by coronaviruses to evade the immune system and initiate infection.
The spikes of the coronavirus play a crucial role in the virus attaching to and entering our cells. A deeper understanding of these proteins is important because they are key factors in interspecies transmission and are major targets of neutralizing antibodies.
In order to penetrate the host cell and release the viral genome, the spike protein must transition from a closed to an open state. This exposes a receptor-binding domain that latch onto the protein receptor required for entry.
For the best-known coronaviruses, those that cause SARS, MERS and Covid-19, the spikes can alternate freely between these two states. However, the spike proteins of other human and animal coronaviruses are only visible in the closed state.
This leads to the idea that most coronavirus spike proteins may not switch randomly between two states, but rather there may be specific biological signals that trigger them to turn on.
To explore this ancient mystery, Lead authors Raoul de Groot and Daniel HurdissResearch from the Department of Virology, Faculty of Veterinary Medicine, Utrecht University, focused on the spike protein of the human coronavirus HKU1, which, like most spike proteins, is only visible in the closed state.
It is estimated that, overall, Four common cold coronaviruses (HKU1, OC43, NL63 and 229E) cause 15% to 30% of respiratory infections each year. Previous research from the lab has shown that the HKU1 spike protein relies heavily on binding to specific sugar molecules, but why this remains unclear.
In this study, the authors found that sugar binding induces the opening of the spike protein and the exposure of the receptor-binding domain, which is required for subsequent entry steps.
The researchers thus discovered biomolecular mechanisms hitherto unknown to science. “This is a finely tuned sugar switch. From the virus’s perspective, it’s a clever way to hide its Achilles’ heel, its receptor-binding domain, until the perfect moment,” Heddis said. Adding: “Our findings paint a more detailed picture of coronavirus binding and the potential use of dual receptors as a means of immune evasion.”