Research Discovers More Door Openers To Cell

Coronavirus SARS-CoV-2 is known to infect cells via the receptor ACE2. An international research team under the coordination of Germany and Finland has identified neuropilin-1 as a factor that promotes the invasion of SARS-CoV-2 into cells. Neuropilin-1 is localized in the respiratory and olfactory epithelium and may be a strategically important localization that contributes to the infectivity and spread of SARS-CoV-2. Experts from the German Center for Neurodegenerative Diseases (DZNE), Technische Universität München, University of Göttingen Medical Center, University of Helsinki, and other research institutes have published their findings in the journal. Science..

The· Coronavirus SARS-CoV-2 affects a variety of organs, such as the lungs and kidneys, and can cause neurological symptoms such as temporary loss of smell and taste. Therefore, the range of symptoms of the related disease known as COVID-19 is very complex. The associated virus, SARS-CoV, was much less common in 2003, probably because the infection was confined to the lower respiratory system, making the virus less contagious. In contrast, SARS-CoV-2 also infects the upper respiratory tract system, including the nasal mucosa, resulting in rapid spread by active viral shedding, such as when sneezing.

Door opener to cell

Tissue tropism reflects the ability of the virus to infect specific cell types in various organs. It is determined by the availability of docking sites on the surface of the cell, the so-called receptors. These allow for cell docking and cell penetration. “The starting point for our research was the question of why SARS-CoV and SARS-CoV-2, which use ACE2 as a receptor, cause different diseases,” said DZNE’s Munich site research group leader, Molecular Neurology. Michael Simmons, a professor of biology, explained that the team was involved in the current study at the Technische Universität München, along with a group of Giuseppe Barristolelli at the University of Helsinki.

To understand how these differences in tissue tropism can be explained, researchers looked at the viral “spike proteins,” which are essential for viral invasion. “The SARS-CoV-2 spike protein differs from its older relatives by the insertion of a furin cleavage site,” Simons explained. “Similar sequences are found in spike proteins of many other highly pathogenic human viruses. This may be the answer when we notice that this furin cleavage site is present in the SARS-CoV-2 spike protein. I wondered if it was. ”When a protein is cleaved by furin, certain amino acid sequences are exposed at the cleaved ends. Such furin-cleaving substrates have a characteristic pattern known to bind to neuropilin on the cell surface.

Experiments using laboratory-cultured cells in combination with artificial and naturally occurring viruses that mimic SARS-CoV-2 show that neuropilin-1 can promote infection in the presence of ACE2. is showing. Infection was suppressed by specifically blocking neuropilin-1 with an antibody. “If you think of ACE2 as the door to cells, neuropyrin-1 can be a factor in guiding the virus to the door. ACE2 is expressed at very low levels in most cells. It’s not easy for the virus. Other factors, such as neuropyrin-1, may be needed to help the virus, “Simons explained.

Potential ways to the nervous system

Scientists examined tissue samples of dead patients because odor loss is a symptom of COVID-19 and neuropilin-1 is found primarily in the cell layer of the nasal cavity. “I wanted to find out if cells equipped with neuropilin-1 were really infected with SARS-CoV-2, and I found this to be the case,” says Simons. Additional experiments in mice have shown that neuropilin-1 allows the transport of small virus-sized particles. Nasal mucosa In the central nervous system. These nanoparticles are chemically designed to bind neuropyrin-1. When the nanoparticles were administered to the animal’s nose, they reached the neurons and capillaries of the brain within hours, in contrast to the control particles, which had no affinity for neuropilin-1. “We could determine that neuropyrin-1 promotes transport to the brain, at least under the conditions of our experiments, but we cannot conclude whether this also applies to SARS-CoV-2. This pathway. Is very likely to be suppressed by the immune system in most patients, “explains Simons.

What is the starting point for future treatments?

“SARS-CoV-2 has an ACE2 receptor cellHowever, other factors, such as neuropyrin-1, may be needed to support that function, “Simons said. “But at this point, we can only speculate on the molecular processes involved. Perhaps neuropilin-1 Virus Then point it at ACE2. Further investigation is needed to clarify this issue. It is currently premature to speculate whether blockade of neuropilin is a viable therapeutic approach. This needs to be addressed in future research. ”