Investigations have found the secret weapon that SARS-CoV-2 uses to be far more infectious than its predecessor coronavirus, SARS-CoV.
With the new discovery, described in an article in the journal Science, new doors are opened to delve into the way in which the virus spreads and to be able to combat it more effectively.
Like its predecessor, the new coronavirus uses the ACE2 receptor to access human cells and rapidly spread through the respiratory system, but with a different receptor protein “hook.”
“The starting point of our study was the question of why SARS-CoV, a coronavirus that caused a much smaller outbreak in 2003, and SARS-CoV-2 spread in such a different way despite using the same main ACE2 receptor, ”says Ravi Ojha, a virologist at the University of Helsinki in Finland.
Researchers from the Technical University of Munich (Germany) and the University of Helsinki examined the spike coating of the virus under a microscope and compared the genomes of the two viruses. They then discovered that the new coronavirus had learned a new trick: to use a kind of ‘grappling hook’ to more aggressively adhere to human tissues, in particular to the neuropilin-1 receptor, which lines the nerve tissues within the cavity. human nasal.
Compared to its predecessor, the new coronavirus had acquired an ‘extra piece’ in its surface proteins, which is also found in the spines of many devastating human viruses, including Ebola, HIV, and highly pathogenic strains of avian influenza. , among others, ”says Olli Vapalahti, a virologist at the Finnish university.
Thus, to infect human cells, SARS-CoV-2 is able to use a receptor called neuropilin-1, which is very abundant in various human tissues, including the respiratory tract, blood vessels, and neurons.
SARS-CoV-2 was known to use the ACE2 receptor to infect our cells, but viruses often use multiple factors to maximize their infectious potential. Unlike the major receptor ACE2, which is present at low levels, neuropilin-1 is very abundant in cells of the nasal cavity.
For his part, Giuseppe Balistreri, head of the Viral Cell Biology research group at the Faculty of Biology and Environmental Sciences of the University of Helsinki, explains that “it is a location of strategic importance that possibly contributes to the efficient ineffectiveness of this new coronavirus, which has caused a great pandemic, which is spreading rapidly throughout the world ”.
To prove their theory, the researchers unfolded antibodies made by cloning white blood cells, and engineered them to block access to neuropilin-1. They then introduced a pseudovirus designed to mimic the behaviors of SARS-CoV-2, and SARS-CoV-2 found it much more difficult to infect cells when neuropilin-1 was blocked.
“If you think of ACE2 as a door lock to enter the cell, then neuropilin-1 could be a factor that directs the virus to the door. ACE2 is expressed at very low levels in most cells. Therefore, it is not easy for the virus to find doors to enter. Other factors such as neuropilin-1 could help the virus find its door, ”says Balistreri.
Additional experiments in mice confirmed the role of the receptor in the access of the virus to its nervous system. The scientists also examined tissue samples from deceased COVID-19 patients to “find out whether cells equipped with neuropilin-1 are actually infected by SARS-CoV-2.”
“We found out that this was the case,” said Mika Simons, professor of molecular neurobiology at the Technical University of Munich and a co-author of the study.
An independent team of scientists from the University of Bristol, UK, has obtained similar results and confirmed that the virus spike binds directly to neuropilin-1.