https://www.sydney.edu.au/news-opinion/news/2023/02/10/scientists-discover-receptor-that-blocks-covid-19-infection.html * Home * News & opinion * News * 2023: all news * February + Scientists discover receptor that blocks COVID-19 infection + Is 13 too young to have a TikTok or Instagram account? + Intermittent fasting leads to weight loss not improved health + What if Opal and Myki became one University home Library Current students Staff intranet Find an event Give Skip to main content * Library * Current students * Staff intranet * Find an event * Give Toggle the side menu University of Sydney Search for Courses University of Sydney University of Sydney Type to search [ ] Search for courses, people, events and everything else ... ( ) Courses ( ) Students ( ) All content Search University of Sydney Study Study Find a course Why choose Sydney? 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Left: Control Lung. Right: Immunofluorescent staining shows expression of new SARS-CoV-2 spike-receptor LRRC15 (green) in post-mortem lung tissue section from individual with COVID-19 [Credit: Loo and Waller et al.] Left: Control Lung. Right: Immunofluorescent staining shows expression of new SARS-CoV-2 spike-receptor LRRC15 (green) in post-mortem lung tissue section from individual with COVID-19 [Credit: Loo and Waller et al.] This protein, the leucine-rich repeat-containing protein 15 (LRRC15), is an inbuilt receptor that binds the SARS-CoV-2 virus without passing on the infection. The research opens up an entirely new area of immunology research around LRRC15 and offers a promising pathway to develop new drugs to prevent viral infection from coronaviruses like COVID-19 or deal with fibrosis in the lungs. The study has been published in the journal PLOS Biology. It was led by Professor Greg Neely with his team members Dr Lipin Loo, a postdoctoral researcher, and PhD student Matthew Waller at the Charles Perkins Centre and the School of Life and Environmental Sciences. The University study is one of three independent papers that reveal this specific protein's interaction with COVID-19. "Alongside two other groups, one at Oxford, the other at Brown and Yale in the USA, we found a new receptor in the LRRC15 protein that can stop SARS-CoV-2. We found that this new receptor acts by binding to the virus and sequestering it which reduces infection," Professor Neely said. "For me, as an immunologist, the fact that there's this natural immune receptor that we didn't know about, that's lining our lungs and blocks and controls virus, that's crazy interesting. "We can now use this new receptor to design broad acting drugs that can block viral infection or even suppress lung fibrosis." What is LRRC15? The COVID-19 virus infects humans by using a spike protein to attach to a specific receptor in our cells. It primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people. Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected. "We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types," Dr Loo said. "Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15," Mr Waller said. LRRC15 is present in many locations such as lungs, skin, tongue, fibroblasts, placenta and lymph nodes. But the researchers found human lungs light up with LRRC15 after infection. "When we stain the lungs of healthy tissue, we don't see much of LRRC15, but then in COVID-19 lungs, we see much more of the protein," Dr Loo said. "We think this newly identified protein could be part of our body's natural response to combating the infection creating a barrier that physically separates the virus from our lung cells most sensitive to COVID-19." Pastel pop art illustration of human lung generated using OpenAI's DALL*E 2 [Credit: Greg Neely] Pastel pop art illustration of human lung generated using OpenAI's DALL*E 2 [Credit: Greg Neely] Implications of the research "When we studied how this new receptor works, we found that this receptor also controls antiviral responses, as well as fibrosis, and could link COVID-19 infection with lung fibrosis that occurs during long COVID," Mr Waller said. "Since this receptor can block COVID-19 infection, and at the same time activate our body's anti-virus response, and suppress our body's fibrosis response, this is a really important new gene," Professor Neely said. "This finding can help us develop new antiviral and antifibrotic medicines to help treat pathogenic coronaviruses, and possibly other viruses or other situations where lung fibrosis occurs. "For fibrosis, there are no good drugs: for example, idiopathic pulmonary fibrosis is currently untreatable." Fibrosis is a condition in which lung tissue becomes scarred and thickened, causing breathing difficulties. COVID-19 can cause inflammation and damage to the lungs, leading to fibrosis. The authors said they are developing two strategies against COVID-19 using LRRC15 that could work across multiple variants - one which targets the nose as a preventative treatment, and another aimed at the lungs for serious cases. The researchers also said that the presence or lack of LRRC15, which is involved in lung repair, is an important indication of how severe a COVID-19 infection might become. "A group at Imperial College London independently found that absence of LRRC15 in the blood is associated with more severe COVID, which supports what we think is happening." Dr Loo said. "If you have less of this protein, you likely have serious COVID. If you have more of it, your COVID is less severe. "We are now trying to understand exactly why this is the case." The research involved screening human cell cultures for genes and investigating the lungs of human COVID-19 patients. --------------------------------------------------------------------- Declaration: Professor Greg Neely is funded by the National Health and Medical Research Council (NHMRC) project grants, the NSW Ministry of Health, and a philanthropic donation from Dr John and Anne Chong. Dr Lipin Loo is funded by a Dr John and Anne Chong Fellowship for Genome Editing and seed funding from the Drug Discovery Initiative at the University of Sydney, and Mathew Waller is funded by a Research Training Program (RTP) Scholarship from the Australian Government. Hero image: Abstract depiction of human fibroblasts and virus generated using OpenAI's DALL*E 2 [Credit: Greg Neely] Philip Ritchie Media and PR Adviser (Science) Mobile * +61 403 149 048 Email * philip.ritchie@sydney.edu.au Related articles Opinion_ 30 June 2022 [0] 'Long COVID' presents a major health challenge - how can Australia be prepared? Triple vaccination seems to reduce the chance of long COVID - but we still need to prepare for a jump in cases, write researchers at the University of Sydney. 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News_ 11 May 2022 Professor Jamie Triccas in lab Partnership to develop 'variant-proof' COVID-19 vaccine The University of Sydney is a lead partner in an international consortium awarded up to US$19.3 million by The Coalition for Epidemic Preparedness Innovations to support the development of a 'variant-proof' SARS-CoV-2 vaccine candidate. next slide previous slide University of Sydney Leadership for good starts here Media * News * Find an expert * Media contacts Student links * How to log in to University systems * Key dates * Class timetables * Policies About us * Our rankings * Faculties and schools * Research centres * Campus locations Connect * Contact us * Find a staff member * Careers at Sydney * Find an event * Emergencies and personal safety Member of Group Of Eight APRU Athena Swan member University of Sydney Twitter University of Sydney Facebook University of Sydney Instagram University of Sydney Youtube University of Sydney Wechat Wechat QR code Follow us_ * Disclaimer * Privacy * Accessibility * Website feedback ABN: 15 211 513 464 CRICOS Number: 00026A TEQSA: PRV12057