SARS-CoV-2 coronavirus can various organs, such as the lungs and kidneys, and also cause neurological symptoms, adding transient loss of smell and taste, so the spectrum of symptoms of the relevant disease, known as COVID-19, is quite complex. A similar virus, SARS-CoV, caused a much smaller outbreak in 2003, perhaps because the infection was limited to decreased respiratory system, making the virus less communicable. SARS-CoV-2, on the other hand, also infects the upper breathing system, adding the nasal mucosa, and therefore spreads rapidly through active viral excretion, e. g. sneezing.
Open door to cell
Tissue tropism reflects the ability of a virus to infect cell types expressed in other organs. It is decided through the availability of host sites, called receptors, on the surface of cells. These allow coupling and penetration into the cells. “The starting point of our study was the question of why SARS-CoV and SARS-CoV-2, which use ACE2 as a receptor, cause other diseases,” explained Mikael Simons, head of the study organization at the site. from the DZNE in Munich and professor of molecular neurobiology. at the Technical University of Munich, whose team has been concerned with ongoing studies, with the Giuseppe Balistreri organization at the University of Helsinki.
To perceive how these differences in tissue tropism can be explained, the researchers observed the viral “complex proteins” that are essential for access to the virus. “The complex protein of SARS-CoV-2 differs from its oldest parent in placing a furine excision matrix,” Simons explained. “Similar series are discovered in the complex proteins of many other highly pathogenic human viruses. When we learn that this furine excision is provided in the PROTEIN of the SARS-CoV-2 complex, we thought it might take us “When proteins are split through furin, an express series of amino acids is exposed to their divided end. Such substrates scinded through furin have a characteristic tendency that is known to join neuropilins on the moving surface.
Experiments using laboratory-cultured cells, along with synthetic viruses mimicking SARS-CoV-2, as well as herbal viruses, imply that neuropiline-1 is able to sell the infection in the presence of ACE2, in particular by blocking neuropiline-1 with antibodies. , the infection was suppressed. ” If ACE2 is a gateway to enter the cell, then neuropiline-1 may also be something that directs the virus to the door. ACE2 is expressed in very low degrees in maximum cells. It is not easy for the virus to locate the entrance doors. Other things like neuropilin-1 may be needed to help the virus,” Simons explained.
A pathway in the nervous system.
Because the loss of odor is one of the symptoms of COVID-19 and neuropilin-1 is discovered mainly in the mobile layer of the nasal cavity, the scientists analyzed tissue samples from deceased patients. “We wanted to know if the mobiles with neuropilin-1 are inflamed with SARS-CoV-2, and he found that to be the case, “Simons said. Additional experiments in mice have shown that neuropilin-1 transports small debris the length of a virus from the nasal mucosa to the central nervous system formula. chemically engineered to bind to neuropilin-1. When nanodebris were administered to the animals’ noses, they reached neurons and capillaries in the brain within hours, unlike control debris with no affinity for neuropilin-1. “We can discover that neuropilin-1, at least in the situations of our experiments, promotes delivery to the brain, however, we cannot draw any conclusions as to whether this is also true for SARS-CoV-2. It is suppressed through of the immune formula in peak patients, “Simons explained.
A starting point for long-term therapies?