2 min readResearchers Discovered the Second ‘Key’ Used by the SARS-CoV-2 Virus to Enter into Human Cells

Helsinki, Finland — To efficiently infect human cells, SARS-CoV-2, the virus that causes COVID-19, is able to use a receptor called Neuropilin-1, which is very abundant in many human tissues including the respiratory tract, blood vessels and neurons. The breakthrough discovery was made by a German-Finnish team of researchers led by neuroscientists Mika Simons ,Technical University of Munich, Germany and virologist Giuseppe Balistreri, University of Helsinki, Finland. 

Why is the new coronavirus so infectious? 

“That SARS-CoV-2 uses the receptor ACE2 to infect our cells was known, but viruses often use multiple factors to maximize their infectious potential” says Dr. Giuseppe Balistreri, head of the research group Viral Cell Biology at the University of Helsinki involved in the study. 

Unlike other respiratory viruses, SARS-CoV-2 infects also the upper respiratory system including the nasal mucosa and consequently spreads rapidly. “This virus is able to leave our body even when we simply breath or talk”, Balistreri adds. “The starting point of our study was the question why SARS-CoV, a coronavirus that led to a much smaller outbreak in 2003, and SARS-CoV-2, spread in such a different way even if they use the same main receptor ACE2”, explains Ravi Ojha, a young researcher in the Balistreri’s team, and one of the main contributors of the study.

A mysterious extra key on the virus surface

To understand how these differences can be explained, in collaboration with the team of Professor Olli Vapalahti, University of Helsinki, the researchers took a look at the viral surface proteins, the spikes, that, like hooks, anchor the virus to the cells. Balistreri reveals that “when the sequence of the SARS-CoV-2 genome became available, at the end of January, something surprised us. Compared to its older relative, the new coronavirus had acquired an ‘extra piece’ on its surface proteins, which is also found in the spikes of many devastating human viruses, including Ebola, HIV, and highly pathogenic strains of avian influenza, among others. We thought this could lead us to the answer”. In collaboration with giant virologist Ari Helenius, ETH Zurich, Switzerland, and cancer biologists Professor Tambet Teesalu, University of Tartu, Estonia, the mystery was solved: the extra key binds to neuropilin-1.

Together, the coordinated team of international researchers, including more than 30 scientists from Germany, Finland, Estonia and Australia, looked at whether neuropilins were important for infection by SARS-CoV-2. Their experiments now support this hypothesis. Interestingly, an independent team of scientists at the University of Bristol , UK, has obtained similar results and confirmed that the virus spike binds directly to neuropilin-1 (Ref. DOI: 10.1126/science.abd3072). The two studies complement each other.

New antiviral strategy in making

By specifically blocking neuropilin-1 with antibodies, the researchers were able to significantly reduce infection in laboratory cell cultures. “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. Thus, it is not easy for the virus to find doors to enter. Other factors such as neuropilin-1 might help the virus finding its door”, says Balistreri. 

Balistreri cautiously concludes “it is currently too early to speculate whether blocking directly neuropilin could be a viable therapeutic approach, as this could lead to side effects. This will have to be looked at in future studies. Currently our laboratory is testing the effect of new molecules that we have specifically designed to interrupt the connection between the virus and neuropilin. Preliminary results are very promising and we hope to obtain validations in vivo in the near future.”

Article adapted from a University of Helsinki news release.

Publication: Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Cantuti-Castelvetri, L et al. Science (October 20, 2020): Click here to view.

ACE2, COVID-19, Neuropilin-1, SARS-CoV-2

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