Neuropilin protein facilitates the entry of Sars-CoV-2 into the cells

It is known that the coronavirus SARS-CoV-2 infects cells via the ACE2 receptor, but the neuropilin protein can do that too. An international research team under German-Finnish coordination has now identified Neuropilin-1 as such a factor. This membrane protein can facilitate the entry of coronaviruses into the cell interior. It is localized in the respiratory and olfactory epithelia. This could be a strategically important location that contributes to the infectivity and spread of COVID-19. Experts from the German Center for Neurodegenerative Diseases (DZNE), the Technical University of Munich, the University Hospital Göttingen, the University of Helsinki and other research institutions have now published their results in the journal Science.

Door opener for infections – Neuropilin protein

neuropilin protein drives the infectivity of sars cov 2 into the cells

The coronavirus can attack various organs such as the lungs and kidneys and thus trigger neurological symptoms. These include a temporary loss of smell and taste. The spectrum of symptoms of the associated disease known as COVID-19 is therefore quite complex. A related virus, SARS-CoV, resulted in a much smaller outbreak in 2003, possibly because the infection was confined to the lower respiratory tract. This made the virus less transmittable. In contrast, SARS-CoV-2 also infects the upper respiratory tract, including the nasal mucosa. As a result, it spreads rapidly through active virus shedding, such as when sneezing.

Investigations on coronavirus in the laboratory covid 19 infection spread

Tropism reflects the ability of a virus to infect certain types of cells in different organs. This is determined by the availability of docking points, so-called receptors, on the surface of cells. The receptors enable docking and penetration into the cells. The starting point of this study was the question of why SARS-CoV and SARS-CoV-2, which use ACE2 as a receptor, cause different diseases. This was explained by Mikael Simons, research group leader at the DZNE site in Munich and professor for molecular neurobiology at the Technical University of Munich. His team was involved in the current studies, together with Giuseppe Balistreri’s group at the University of Helsinki.

Study results

neuropilin protein drives the infectivity of sars cov 2 into the cells

To understand how these differences can be explained, the researchers examined the viral “spike proteins”. This is because these are essential for the virus to enter. The SARS-CoV-2 spike protein differs from its older relative by the insertion of a furin cleavage site. This is how Simons explained this process. Similar sequences are found in the spike proteins of many other highly pathogenic human viruses. When proteins are cleaved by furin, a specific amino acid sequence is exposed at their cleaved end. Such furin-cleaved substrates show a characteristic pattern. This is known to bind to a neuropilin protein on the cell surface. Experiments with cells cultivated in the laboratory in connection with artificial viruses that mimic SARS-CoV-2, as well as naturally occurring viruses, show that Neuropilin-1 can promote infection in the presence of ACE2. The infection was suppressed by specifically blocking Neuropilin-1 with antibodies.

scientist analyzes blood samples from infected patients with covid 19 and x-rays

Additional experiments on mice showed that Neuropilin-1 enables the transport of tiny virus-sized particles from the nasal mucosa to the central nervous system. These nanoparticles were chemically engineered to bind to Neuropilin-1. When the nanoparticles were administered to the animals’ noses, they reached neurons and capillaries in the brain within a few hours. It is very likely that such a pathway will be suppressed by the immune system in most patients. Presumably, Neuropilin-1 intercepts the virus and forwards it to ACE2. Further research is needed to clarify this issue. It is too early to speculate at this point whether blocking Neuropilin is possible. To this study Such a therapeutic approach would be very practicable for medicine and should be taken into account in future studies.