新冠病毒 z-bo 2020-10-22 361

　　The new coronavirus SARS-CoV-2 causes the 2019 Coronavirus Disease (COVID-19) and is now raging around the world. As we all know, SARS-CoV-2 infects host cells through the receptor ACE2. In a new study, researchers from the German Research Center for Neurodegenerative Diseases, the Technical University of Munich, the University of Göttingen Medical Center, and the University of Helsinki in Finland found that neuropilin-1 (NRP1) is A factor that can promote SARS-CoV-2 to enter cells. NRP1 is located in the respiratory tract and olfactory epithelium, which may be an important strategic positioning, but it helps the infection and spread of SARS-CoV-2.

　　SARS-CoV-2 can affect multiple organs such as the lungs and kidneys, and can also cause neurological symptoms, including temporary loss of smell and taste. Therefore, the symptom spectrum of COVID-19 is quite complex. In 2003, a related coronavirus---SARS-CoV-- caused a much smaller outbreak. This may be because the virus infection was limited to the lower respiratory system, making the virus less spread. On the contrary, SARS-CoV-2 will also infect the upper respiratory system, including the nasal mucosa, so it will spread rapidly through active virus shedding (such as when sneezing).

　　the door opener into the cell

　　Tissue chemotaxis reflects the ability of viruses to infect specific cell types in different organs. It depends on whether there are docking points on the cell surface, the so-called receptors. These receptors allow the virus to dock and invade the cell. Simons explained, ""The starting point of our research is why SARS-CoV and SARS-CoV-2, which both use ACE2 as a receptor, cause different diseases. "

　　In order to understand the differences in the tropism of these tissues, these researchers observed the "spike protein" of SARS-CoV-2, which is the key to the virus entering the host cell. Simons explained, "The difference between the SARS-CoV-2 spike protein and its older relatives is that it inserts a furin cleavage site. In the spikes of many other highly pathogenic human viruses A similar sequence was also found in the protein. When we realized that this furin cleavage site exists in the SARS-CoV-2 spike protein, we thought it might lead us to find the answer. "When the protein is furin When it is cleaved, a specific amino acid sequence is exposed at its cleaved end. Such a protein substrate that can be cleaved by furin has a characteristic pattern sequence known to bind to neuropilin on the cell surface.

　　Experiments using laboratory-cultured cells, artificial viruses that mimic SARS-CoV-2, and naturally-occurring viruses have shown that in the presence of ACE2, NRP1 can promote viral infection. By specifically blocking NRP1 with antibodies, this viral infection can be suppressed. Simons explained, “If you think of ACE2 as a door into the cell, then NRP1 may be a factor that guides this virus into this door. The expression level of ACE2 in most cells is very low. Therefore, this It’s not easy for a virus to find its way into the cell. Other factors such as NRP1 may be necessary to help this virus enter the cell."

　　A potential way into the nervous system

　　Given that loss of smell is one of the symptoms of COVID-19, and NRP1 is mainly present in the cell layer of the nasal cavity, these researchers examined tissue samples from dead patients. Simons said, "We wanted to find out whether the cells expressing NRP1 were actually infected by SARS-CoV-2, and found that this was indeed the case." Other experiments in mice showed that NRP1 can remove virus-sized nanoparticles from the nasal mucosa. Transport to the central nervous system. These nanoparticles are chemically engineered to bind to NRP1. In contrast to control particles that have no affinity for NRP1, when these NRP1-binding nanoparticles are applied to the noses of these mice, they reach the neurons and capillaries in the brain within a few hours. Simons explained, “We can be sure that, at least under our experimental conditions, NRP1 can promote the transport of these nanoparticles to the brain, but we cannot draw any conclusions about whether this is also the case for SARS-CoV-2. Very much. It is possible that in most patients, this transport route is suppressed by the immune system."

　　A starting point for developing new therapies in the future?

　　Simons said, “SARS-CoV-2 requires ACE2 receptors to enter cells, but it may require other factors such as NRP1 to support its function. However, we can only speculate about the molecular processes involved. According to our speculation, NRP1 captures This virus directs it to ACE2. Further research is needed to clarify this problem. It is too early to speculate whether blocking NRP1 can be a viable treatment. This must be addressed in future studies. ."