Five researchers from Cornell University in Ithaca, New York, set out to learn more about the structure and mechanisms related to two coronaviruses that have created turmoil in the past. These are SARS-CoV, the virus that can lead to severe acute respiratory syndrome (SARS), and MERS-CoV, which can trigger Middle East respiratory syndrome (MERS).
But in the context of the current COVID-19 pandemic, the scientists — Tiffany Tang, Miya Bidon, Javier Jaimes, Ph.D., Gary Whittaker, Ph.D., and Prof. Susan Daniel — soon turned their attention to the new coronavirus, SARS-CoV-2.
In their initial, as well as current research, the investigators were particularly interested in the function of the spike protein. This is a protein that viruses use to transfer their genetic information into cells, causing infection.
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The investigators now report their findings in the journal Antiviral Research.
In their research, the scientists looked, specifically, at fusion peptides, short-chain amino acids present in the spike proteins of the coronaviruses that they were studying.
To infect a cell, the viruses go through a multistep process called “membrane fusion,” which ultimately allows them to “inject” their genetic information into the cell they are infecting.
Membrane fusion happens once the virus locates a cell that is susceptible to infection. The virus does this by taking chemical cues from its environment. Finally, the virus attaches to the receptor of the target cell via the spike protein.
At this point, the fusion peptide, which is a part of the spike protein, merges with the cell membrane. This forms an opening that allows the virus to transfer its genetic material into the cell. This will ensure that the virus can replicate.
The researchers found that calcium ions help the fusion peptide to “do its job” and allow coronaviruses — specifically MERS-CoV and SARS-CoV — to infect cells.
A comparison between the fusion peptides of the different coronaviruses found that the biological sequences of the fusion peptides present in SARS-CoV and SARS-CoV-2 were 93% alike.
This could mean that the mechanism affecting their fusion peptides are also very similar.
“What’s really interesting about SARS-CoV and MERS-CoV, and this new virus, SARS-CoV-2, is this particular part of the protein, the fusion peptide, is almost exactly the same in those three viruses,” says Prof. Daniel.
The researchers now hope that their current findings will help scientists understand more about how SARS-CoV-2 can infect humans, and why the human respiratory tract seems to provide such a suitable environment for this virus to replicate.
Moreover, the investigators have now managed to secure funding from the National Institutes of Health (NIH) in support of their efforts to develop an antibody that might stop the virus from replicating by acting on its fusion peptide.
“Blocking the fusion step is significant because the fusion machinery doesn’t evolve and change as fast as other parts of the protein do. It’s been built to do a particular thing, which is to merge these two membranes together. So if you can develop antiviral strategies to reduce that efficiency, you could have potentially very broadly-acting treatments.”
– Prof. Susan Daniel
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