Multiple articles reveal the weakness of SARS-CoV-2 protrusion protein

May 31, 2020 /
Bio-Valley
BIOON/--- coronavirus, i.enodule protrusions protruding outwards in all directions: protrusion proteins, which are also the key to its entry into the cellThese protoproteins bind to cells--- in the case of SARS-CoV-2, they bind to human cells--- causing infectionTo prevent this from happening, scientists around the world are looking at protrusion proteins to reveal how they work and to find potential weaknesses to exploit themA transmission mirror image of SARS-CoV-2 (formerly known as 2019-nCoV) from NIAID RMLthis protrusion structure itself is actually a protoprotein tripolymerA site at the top of the protrusion structure allows SARS-CoV-2 virus particles to bind to an enzyme called ACE2 receptor on the surface of human cells, says Rommie Amaro, a biophysical chemist at the University of California, San Diego, the site must be in an "open" or "upward" position, bent and ready to bind itself to the host cell receptorAn animation posted online by biophysicist Greg Bowman of the University of Washington School of Medicine shows what looks like a creature opening its chinBut Amaro says that in many of the images of SARS-CoV-2 protrusion structures that have been produced so far, an important feature is largely missingthis protrusion structure is covered with sugars called polysaccharidesThey are thought to allow the coronavirus to disguise the human immune system, making it look like a harmless cell, which is often covered with sugarIn this image of the coronavirus protrusion structure and three-dimensional models, These sugars are often represented as small, coarse protrusions, but in fact they are more blurred and hindering than this, Amaro saidshe explains, "They protect it like physical shields." "In fact, these polysaccharides are so protective that the protoproteins may have to bend and extend simply to pass through these polysaccharides and bind to ACE2 on the surface of human cellsAny antibodies that target the protrusion structure must be inserted between these polysaccharides and bound to the protrusion protein itself to simulate which defensive polysaccharides are covered with SARS-CoV-2 protrusion proteins, Amaro used mass spectrometry data from the protoprotein, which was published on March 28 on the preprint server bioRxiv This reveals the location of these polygrides in more detail than before An animation recently posted online by Amaro shows how these polyglycings are wrapped in the protrusion protein and wiggling, which could further affect their ability to hold antibodies out of the protrusion structure In this animation, the protoprotein protrudes from the lipid membrane of the coronavirus Chris Oostenbrink, a molecular modeling expert at the Austrian University of Natural Resources and Life Sciences, is doing similar research His method, he explains, involves using a polysaccharide-shaped database and matching it to the shape of the protruding structure of a known coronavirus--- which is a molecular puzzle he said, "Basically, we put them all up, and we chose the most appropriate model for the representative." One of the images created by his graduate student, Jan Walther Perthold, shows the polysaccharides covering the bursting structure as a fuzzy ball Like Amaro's model, this reveals how common these polysaccharides are, and they pose a serious barrier to any antibodies that may bind to the protrusion structure By mapping the polysaccharide shield, or polysaccharide barrier, it should make it easier for scientists to find suitable antibodies to pass through the pores of the polysaccharide barrier, Amaro said For example, a vaccine could be designed to stimulate the body's immune system to produce antibodies that successfully bind to the protrusion structure, disrupt its open mechanism, or otherwise prevent it from binding to ACE2 Amaro suggests that it can be imagined as stuffing a wrench into a machine and stopping it study, published April 3 in the journal Science, showed that a special antibody called CR3022 binds to SARS-CoV-2 protrusion proteins The antibody was isolated from a SARS patient as early as 2006 and is better able to target the SARS-CoV virus that led to the 2003 SARS outbreak in laboratory tests, researchers mixed the antibody with SARS-CoV or SARS-CoV-2 in vitro The antibody failed to neutralise SARS-CoV-2, indicating that it was not strongly bound to the new coronavirus After all, it is an older weapon and is not specifically targeted at SARS-CoV-2 targets the authors of the science paper write that they believe the antibody may still be effective in the body, but more trials are needed to prove it Jeremy Rossman, a virologist at the University of Kent in the UK, was not involved in the study He noted that the data show how CR3022 antibodies bind to the protein slightly below the site where the SARS-CoV protrusion protein binds to the host cell This means that it is clearly not functioning by physically blocking binding He added, "It is not clear how this antibody neutralises and blocks the virus." 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perhaps more promising, the researchers found that antibodies isolated from the llamas were better neutralised in combination with human antibodies, a two-pronged attack." In a paper published March 28 in bioRxiv, a preprint server, they wrote that this specially designed double antibody effectively blocks infection by binding to binding sites at the top of the protrusion structure of the host cell the authors also suggest that the spray can be used to treat patients in hale In this way, these antibodies can be inhaled "directly to the site of infection." there are other ways Some pharmaceutical companies have launched projects to develop laboratory cloned antibodies For example, GlaxoSmithKline is using antibodies isolated from a SARS patient to determine whether they are effective in fighting COVID-19 Antibodies or other molecules may also block the SARS-CoV-2 virus in other targeted protrusion structures For example, they can prevent the human body from interacting with the new coronavirus This would be useful because researchers believe that the Flynn protease helps separate the two sub-s of this protrusion structure--- a process that allows the virus to break open and enter the host cell Flynn proteases happen to be abundant in the human body, which means we provide an ideal infection environment for SARS-CoV-2 There may be molecules that isolate flynn proteases from the virus, which may prevent the pathogen from entering the body Some teams are currently evaluating whether Flynn protease inhibitors can do this 'No matter what method we target the proteoid protein, we need to be careful, ' says Akiko Iwasaki, an immune biologist at Yale University School of Medicine in the Scientists must determine which antibodies bind to the protrusion structure, but also make sure they do not trigger a bad immune response at the same time She points out that a paper published last year in the journal JCI Insight showed that antibodies in monkeys infected with SARS-CoV sometimes exacerbate disease rather than calm it in macaques, an anti-protosconoid protein antibody stimulates blood cells called macrophages, causing inflammation in the lungs of the primate The authors note that patients who die from SARS have similar lung inflammation "I'm worried that this could be the case in SARS-CoV-2," Iwasaki said The really serious illness won't happen in two weeks And that's when the antibody appears Rossman said that if scientists can find antibodies that do not trigger a dangerous immune response, it is possible to provide them to infected patients to help them beat COVID-19 But it would be better if we could find a peptide that would promote the production of these antibodies so that patients could be immunized before they became infected (Bio Valley Bioon.com) Reference: 1.Yasunornowatabe et al.
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