COVID-19 Latest: Research Indicates That Glycans Could Be The Answer In Reining In The Sars-CoV-2 Coronavirus
Source: COVID-19 Latest Sep 24, 2020 4 years, 1 month, 3 weeks, 6 days, 19 hours, 45 minutes ago
COVID-19 Latest: Researchers from University of California-San Diego, University of Texas-Austin and Maynooth University-Dublin have discovered an active role for glycans, the sugar molecules that decorate the spike proteins of the coronavirus in terms of the actual infection and binding process to human host receptors.
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These glycans in turn could be new targets for certain therapies, and this could also help experts developing vaccines for COVID-19.
https://pubs.acs.org/doi/abs/10.1021/acscentsci.0c01056
The research findings were published in the journal: ACS Central Science.
At the moment, many researchers are focused on the coronavirus spike protein, which binds to the angiotensin-converting enzyme 2 (ACE2) on human cells.
It has been found that before the spike protein can interact with ACE2, it has to change its shape to expose its receptor binding domain (RBD). Similar to other viral proteins, the coronavirus spike protein has a thick coat of glycans on its surface.
It is known that these particular glycans help shield the viral proteins from the host’s immune system.
Professor Dr Rommie Amaro and colleagues at University of California San Diego, Maynooth University and the University of Texas at Austin looked into whether certain glycans in the coronavirus spike protein were also “active players” in the process leading up to an infection.
In order to draw their conclusions, they built molecular dynamics simulations of the coronavirus spike protein embedded in the viral membrane.
Interestingly computer models showed that N-glycans connected to the spike protein at certain sites (N165 and N234) helped stabilize the shape change that exposes the RBD. In addition, the simulations also found regions of the spike protein that weren’t coated by glycans, and could therefore be vulnerable to antibodies.
Dr Amaro told Thailand Medical News, “Overall, this research presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development.”
Significantly this is just one of the latest coronavirus breakthroughs made as of late. On Sept. 17, research from the Francis Crick Institute that was published in the journal Nature
suggested that the spike protein on the surface of the coronavirus can adopt at least 10 distinct structural states. Specifically, this can occur when it is in contact with ACE2.
https://www.thailandmedical.news/news/coronavirus-latest-study-shows-spike-protein-on-the-surface-of-sars-cov-2-can-adopt-at-least-ten-distinct-structural-states-when-in-contact-with-ace2
To date the exact nature of the ACE2 binding to the SARS-CoV-2
spike remains unknown. However, this was the first trial to specifically look at the binding mechanism between ACE2 and the spike protein in its entirety.
The study team determined that after ACE2 binding at a single open site; the spike protein becomes more open, priming it for additional binding. After the spike has been bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus fuse to the cell membrane and cause infection.
Dr Antoni Wrobel, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick further added, "As we unravel the mechanism of the earliest stages of infection, we could expose new targets for treatments or understand which currently available anti-viral treatments are more likely to work.”
The study team note that they are continuing to examine the structures of spikes of SARS-CoV-2 and other related coronaviruses in other specimens. The goal is to better understand the mechanism of viral infection.
Professor Dr Steve Gamblin, group leader of the Structural Biology of Disease Processes Laboratory at the Crick commented, "There's so much we still don't know about SARS-CoV-2, but its basic biology contains the clues to managing this pandemic. By understanding what makes this virus distinctive, researchers could expose weaknesses to exploit."
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