It has been 17 years since the SARS-CoV coronavirus threatened to develop into a global pandemic. With swift efforts to contain outbreaks, the world's population has escaped the worst.
We were out of luck this time. What makes SARS-CoV-2 so much more infectious than its predecessor is a question we can now answer as researchers are discovering another way for the virus to enter our cells.
Researchers at the Technical University of Munich in Germany and the University of Helsinki in Finland have conducted a study that discovered a receptor called neuropilin-1, which enables the new coronavirus to infect our tissues.
This particular protein is relatively abundant in the cells lining the nasal cavity, so it is not difficult for the virus to settle in our bodies, multiply and then spread to a new host.
Earlier this year, it was discovered that a receptor called angiotensin converting enzyme 2 (ACE2) helps the coronavirus bind to the surface of cells, while an enzyme called transmembrane type II serine protease (TMPRSS2) is critical for its entry.
This kind of molecular hacking well explains why both SARS coronaviruses damage a range of tissues in our body, from the lining of the lungs to the digestive tract.
But it doesn't say why one of the viruses spreads better than the other.
'The starting point of our study was why SARS-CoV, the coronavirus that led to a local outbreak in 2003, and SARS-CoV-2 spread in such different ways, even though they share the same major ACE2 receptor,' says virologist from the University of Helsinki Ravi Ohha.
An important piece of the puzzle came up when comparing the two viral genomes; SARS-CoV-2 has matched the sequences responsible for the formation of a spiny set of 'hooks', not unlike those used by other dangerous pathogens to capture host tissue.
'Compared to its predecessor, the new coronavirus has acquired an' extra chunk 'on surface proteins that is also found in the thorns of many destructive human viruses, including Ebola, HIV and highly pathogenic strains of avian influenza, among others,' 'says Olli Vapalahti, also a virologist at University of Helsinki.
“We thought it might lead us to an answer. But how?'
In consultation with colleagues around the world, the researchers settled on neuropilin-1 as a common factor.
Typically, this receptor plays a role in the response to growth factors important for tissue development, especially nerves. But for many viruses, it is a comfortable handle, allowing the host cells to be held long enough to get inside.
Electron microscopy of the spikes on the surface covering the SARS-CoV-2 particles certainly hinted at the possibility of binding to the receptor.
To confirm this, the researchers used monoclonal antibodies specially selected to block access to neuropilin-1.
Of course, the 'pseudoviruses' containing the SARS-CoV-2 proteins found it much more difficult to get inside when neuropilin-1 was blocked.
“If you think of ACE2 as a door lock to enter a cell, then neuropilin-1 may be the factor that directs the virus to the door,” says Vapalahti.
'ACE2 is expressed at very low levels in most cells. Thus, it is not easy for the virus to find the doors to enter. Other factors, such as neuropilin-1, can help the virus find its door. '
Considering that neuropilin-1 is expressed in large amounts in the nerve tissues of the nasal cavity, we can imagine that for SARS-CoV-2, a carpet roll unfolds as soon as the infection enters the nose.
A closer look at tissue samples that express neuropilin-1 from deceased COVID-19 patients raised suspicions, and an experiment in mice helped confirm the receptor's role in promoting virus entry into our nervous system.
“Our laboratory is currently studying the effects of new molecules that we have specially developed to interrupt the connection between the virus and neuropilin,” says Vapalahti.
This research was published in the journal Science.
Sources: Photo: SARS-CoV-2 'Spike' (red) attaches to neuropilin (blue). (G.Balistreri & secondbaystudio.com)
