eLife: SARS-CoV-2 stingproteins have a common sequence with human proteins

JUNE 11, 2020 /PRNewswire/ -- Earlier this year, scientists determined that there is a cutting site in the SARS-CoV-2 protrusion protein, where the protrusion protein splits into two sub-basesThis division is thought to help break the virus and allow it to enter human cellsIn a recent paper published in the journal eLife, the researchers found that the Flint protease cut site of the protrusion protein is the same as in a sequence in the human epithelial sodium channel, which must also be cut off by Flynn protease to be activatedThe authors suggest that the virus may compete with the sodium channel and may interfere with its function, but this has yet to be proven"This paper is really good because it leads to the general idea that many viruses use certain parts of human cells to help them survive," said David Perlin, who studies infectious diseases and is chief scientific officer at the Meridian Center for Health Discovery and Innovation in Hackensack, New JerseyHe was not involved in the studyPhoto Source: The Scientist's discovery came as researchers at artificial intelligence company nference began studying the presence of surprising or unusual amino acid sequences in the SARS-CoV-2 proteinVenky Soundararajan, chief scientific officer of nference, said the sequence was found in the 10,967 tetraamino acid sequences of the SARS-CoV-2 sting protein published worldwide, but not in the sequence of related coronavirus proteins, such as SARS-CoV or coronaviruses infected with bats or pangolinsOther research groups reported in February and April that the insertion formed a cutting site for human fluorinprotease, which is thought to cut off two subcells of the stingprotein to facilitate entry into human cellsSoundararajan and his colleagues further confirmed this view by determining that the cutting site of fluorinase was the same as that of the confirmed cut site sequence of fluorinn protease in alpha subkeys of the human epithelial sodium channelAlpha-yaji plays a role in regulating salt and liquid balance in many cells of the bodyThis site is essential in the process of assembling the sub-bases of the channel into a functional whole that can regulate sodium levels in cellsNext, the researchers turned to the platform they developed, which used a database of single-cell RNA expression data from 65 previously published human and mouse studies to study gene expression in sodium channels and other human genes known to be associated with SARS-CoV-2 infectionThey found that the expression of the epithelial sodium channel gene overlapped with the expression of the flurinn protease gene and the main SARS-CoV-2 receptor ACE2 gene, which is the type of cell most affected by the virusThe overlap of ACE2, the epithelial sodium channel, and fluorinprotease (fluorinproteinase in nasal, respiratory, and intestinal epithelial cells) supports the idea that these areas are the initial center of human infection, Soundararajan saidPerlin cautions against making assumptions about the abundance of ACE2 based on transcription levels"From gene expression to assembly on cell membranes, we have to be careful at all, " he said"Based on this RNA co-expression, the authors hypothesize that during SARS-CoV-2 infection, the viral pyridoxprotein may compete with human sodium channels against flurinoperaseIf this competition interferes with the activation of the sodium ion channel, the sodium ion channel becomes dysfunctional, affecting its role in regulating the liquid balanceThis may explain why PATIENTS WITH COVID-19 sometimes leave large amounts of fluid in their lungsThe study was "all computationally based and did not experiment." Therefore, we do not have any information to justify the author's suggestionVincent Racaniello, a virologist at Columbia University, warned that he was not involved in the workHe also questioned the idea that the cutting of SARS-CoV-2 pyrous protein may replace the cutting of the epithelial sodium channel in human fluorinaseWe also don't know if the sodium channel is downgraded during the virus infectionHowever, if a virus with a higher affinity of fluorinase in these sodium ion channels is present in the same region, or a high viral load, it is possible that the proportion of sodium ion channel alpha sub-sub-cut will decrease, which may affect the function of local sodium ion channels"Is that so?" says PerlinI'm not sure, but this is an interesting assumption"Most computational analysis requires some experimental validation," said Dario Ghersi, a computational biologist at the University of Nebraska-Omaha who was not involved in the study"This identification site is present in most SARS-CoV-2 isolates, which means that it is important for the virus, which means that the sequence may be meaningful for vaccine and therapeutic development." Their findings seem to me quite reliable(BioValleyBioon.com) References: SARS-CoV-2 Spike Protein Shares With a Human ProteinPAnand et al., "SARS-CoV-2 Strategically-2 Salolytic sphototic activation of human ENaC," eLife, doi: 10.7554/eLife.58603, 2020.