The second 'key' used by the SARS-CoV-2 virus to enter into humans discovered!

The second 'key' used by the SARS-CoV-2 virus to enter into humans discovered!

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.

"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 the head of the research group.

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", the author 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 one of the main contributors of the study.

To understand how these differences can be explained, the researchers took a look at the viral surface proteins, the spikes, that like hooks, anchor the virus to the cells. The author 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". The mystery was solved: the extra key binds to neuropilin-1.

Together, the coordinated team of international researchers looked at whether neuropilins were important for infection by SARS-CoV-2. Their experiments now support this hypothesis. Interestingly, an independent team of scientists has obtained similar results and confirmed that the virus spike binds directly to neuropilin-1. The two studies complement each other.

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 the author.

The author 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."