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This research begins with the ACE2 receptor, a protein in human cells that allows SARS-CoV-2, the virus that causes COVID-19, to enter and infect cells. But now we enter a new pair of elements – other proteins – that exist in human cells.
The combination of these three proteins – two humans and one virus – increases the ability of SARS-CoV-2 to enter human cells, replicate and cause disease.
COVID-19 itself has crippled health care systems and economies around the world. Great efforts are being made to develop vaccines and other therapies to combat this virus. But for these efforts to be successful, understanding how viruses enter cells is critical.
To that end, in two papers published in Science, the two teams independently found that a protein called the neuropilin-1 receptor is an alternative gateway for SARS-CoV-2 to enter and infect human cells. This was a major breakthrough and a surprise, because scientists thought neuropilin-1 was instrumental in helping neurons make the correct connections and aiding blood vessel growth.
Prior to this new study, no one suspected that neuropilin-1 could be a gateway for SARS-CoV-2 to enter the nervous system. Fellow researchers are excited about this report because as neuroscientists studying how pain signals are triggered and sent to the brain, they are also investigating neuropilin-1 activity.
In a recent paper, their team demonstrated how neuropilin-1 is involved with pain signals and how, when the SARS-CoV-2 virus attaches to it, it blocks pain transmission and relieves pain. New work suggests neuropilin-1 is an independent gateway for the COVID-19 virus to infect cells. The findings provide insights that could reveal how to block viruses.
Neuropilin-1 Helps SARS-CoV-2 Enter
A protein called Spike that sits on the outer surface of SARS-CoV-2, which allows the virus to attach to protein receptors in human cells. Realizing that this tiny piece of Spike was similar to a region of a human protein sequence known to bind to neuropilin receptors, the two research teams realized that neuropilin-1 may be important for infecting cells.
Using a technique called X-ray crystallography, which allows researchers to see the three-dimensional structure of the Spike protein at the resolution of individual atoms, as well as other biochemical approaches, James L Daly of the University of Bristol and colleagues demonstrated this short sequence of Spike attached to neuropilin- 1.
In laboratory experiments, the SARS-CoV-2 virus was able to infect fewer human cells lacking neuropilin-1. In cells with ACE2 and neuropilin-1 proteins, SARS-CoV-2 infection was greater than in cells with only one “door”.
Daly and colleagues showed SARS-CoV-2 could infect fewer cells if they used a small molecule called EG00229 or an antibody to block the Spike protein’s access to neuropilin-1.
Neuropilin-1 Receptors Help Viruses Infect Cells
Using a similar method, a team led by German and Finnish researchers came to the same conclusions as the first study. In particular, the team demonstrated that neuropilin-1 is essential for the SARS-CoV-2 virus to enter and infect cells.
By using antibodies to block a single region of the neuropilin-1 receptor protein, the researchers showed SARS-CoV-2 harvested from COVID-19 patients could not infect cells.
In another experiment, Ludovico Cantuti-Castelvetri of the Technical University of Munich and colleagues attached silver particles to a synthetic Spike protein made in the laboratory. As a result, they found that these particles can enter cells that carry neuropilin-1 on their surface.
When they performed the same experiment on live mice, they found that silver particles entered the cells lining the nose. The researchers were surprised to find that the Spike protein could also enter neurons and blood vessels in the brain.
Using tissue from human autopsy, Cantuti-Castelvetri and colleagues noted that neuropilin-1 is present in cells lining the human respiratory tract and nose, whereas the ACE2 protein is not. This suggests that neuropilin-1 provides an independent door for the COVID-19 virus to infect cells.
In addition, the cells lining the nasal passages of COVID-19 patients who were positive for neuropilin-1 were also positive for the Spike protein. These findings confirm that Spike used the neuropilin-1 protein to infect human cells in parts of the body lacking ACE2.
Neuropilin-1 May Block Viruses, Cancer, and Pain
In a surprising discovery recently reported by the lab Live Sciencce, they found the SARS-CoV-2 Spike protein to have pain-relieving effects. Even more surprising is the finding that this analgesia involves the neuropilin 1 receptor.
Live Science demonstrated that Spike prevents a protein from binding to neuropilin-1, which blocks signaling and relieves pain. That’s because when this protein, called Vascular Endothelial Growth Factor A (VEGF-A) – which is produced by many cells in the body – binds to neuropilin-1 under normal circumstances, it initiates the pain signaling process by pulling neurons that convey pain messages.
So, the virus reveals to us a potential new target — the neuropilin-1- receptor for managing chronic pain. Now if we can decipher how neuropilin-1 contributes to pain signaling, then we can target it to devise ways to block pain. (Also read:Jokowi Judged as Lacking Democratic, Democrats Touched Abuse of the ITE Law)
(iqb)
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