This time we were not so lucky. Just what makes SARS-CoV-2 much more contagious than its predecessor is a question we’re now a little closer to solving, with researchers showing yet another way in which the virus enters our cells.
Researchers at the Technical University of Munich in Germany and the University of Helsinki in Finland led a study in which a receptor called neuropilin-1 was discovered, which gives the novel coronavirus a leg-up in infecting our tissues.
This particular protein is relatively abundant on cells lining the nasal cavity, forming a piece of the virus to establish a home inside our body, growing a virus family, and then spreading to a new host is.
Earlier this year it was discovered that a receptor called angiotensin-converting enzyme 2 (ACE2) helps bind coronoviruses to the surface of cells, while an enzyme type II transmemarin serine protease (TMPRSS2) is critical for its entry. .
Such molecular lock-picking does a good job of explaining that both SARS coronaviruses wreak havoc in our lungs from the lining of our digestive system to a range of our body tissues.
But this does not say why one virus does a better job of spreading than another.
“The starting point of our study was the question of whether SARS-COV, a coronovirus that caused very few outbreaks in 2003, and SARS-COV-2, spread even though they use AC main 2” , Says virologist Ravi Ojha of the University of Helsinki.
An important piece of the puzzle appeared on the comparison of the two viral genomes; SARS-CoV-2 had picked up the sequences responsible for the creation of a prickly array of ‘hooks’, not unlike those used by other nasty pathogens to create a grip on the host’s tissues.
“Compared to its old relative, the new coronovirus had gained an ‘extra fragment’ on its surface protein, which is also found in many devastating human virus spikes, including Ebola, HIV, and others in excessive of avian influenza. There are pathogenic strains., Says Oli Vapapalti, also a virologist from the University of Helsinki.
“We thought it might give us the answer. But how?”
In consultation with colleagues around the world, researchers zeroed in on neuropiline-1 as a common factor.
Typically, this receptor plays a role in response to important growth factors in tissue development, especially between nerves. But for many viruses, it is a convenient handle for long-term breakdown on host cells.
Electron microscopy of SARS-CoV-2 particles coating the surface spikes certainly indicated potential for bonding with the receptor.
To help confirm this, researchers chose the use of monoclonal antibodies specifically to block access to the garden variety Neuropilin-1, but not to mutant varieties tweaked to have a different structure.
Surely enough, the ‘pseudovirus’ SARS-CoV-2 protein (great for looking at viruses that enter cells without worrying about the whole messy replication business) went in when neuropilin-1 was shut down. I had a very difficult time.
“If you think of ACE2 as a door lock to enter the cell, then neuropilin-1 may be a factor that directs the virus to the door,” says Ballisterri.
“ACE2 is expressed at a very low level in most cells. Thus, it is not easy for viruses to find doors to enter. Other factors such as neuropilin-1 may help the virus find its door.”
With neuropilin-1 expressed in large amounts in neural tissues within the nasal cavity, we can imagine that SARS-CoV-2 has a convenient red carpet that sniffs an infected drop.
A close suspicion was revealed on tissue samples expressing neuropilin-1 taken from deceased COVID-19 patients, while an experiment involving mice showed the role of the receptor in aiding the entry of the virus into our nervous system to be confirmed.
Whether this can help explain why SARS-CoV-2 infection can have such a traumatic effect on brain function is a question of future research.
“We can determine whether neuropiline-1 promotes transport in the brain, at least under the conditions of our experiments, but we cannot draw any conclusion whether this is true for SARS-CoV-2 as well Is. It is very likely that this is the route. In most patients the immune system is suppressed, “says neurologist Micah Simons from the Technical University of Munich.
It is enticing to depict new forms of antiviral medicine on the horizon. Although the speed with which SARS-CoV-2 reveals its criminal talents, simply shutting down cell receptors is likely to be bad news for our health.
This is to say that discovery is not without opportunity.
“Currently our laboratory is testing the effect of new molecules that we have specifically designed to disrupt the association between viruses and neuropilins,” says Ballisterri.
“Initial results are very promising and we hope to get verification In vivo In the near future.”
This research was published in Science.