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A protein in the lung could form a natural protective barrier to SARS-CoV-2 in humans, as reported by University of Sydney scientists in .

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 a 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 to help deal with fibrosis in the lungs. The researchers screened human cell cultures for genes and investigated the lungs of human COVID-19 patients.

The study 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鈥檚 interaction with COVID-19.

鈥淎longside 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,鈥� Neely said.

鈥淔or me, as an immunologist, the fact that there鈥檚 this natural immune receptor that we didn鈥檛 know about, that鈥檚 lining our lungs and blocks and controls virus, that鈥檚 crazy interesting.

鈥淲e can now use this new receptor to design broad-acting drugs that can block viral infection or even suppress lung fibrosis.鈥�

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.

鈥淲e 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,鈥� Loo said.

鈥淏asically, the virus is coated in the other part of the Velcro, and while it鈥檚 trying to get to the main receptor, it can get caught up in this mesh of LRRC15,鈥� Waller added.

LRRC15 is present in many locations such as lungs, skin, tongue, fibroblasts, placenta and lymph nodes. The researchers found human lungs light up with LRRC15 after infection.

鈥淲hen we stain the lungs of healthy tissue, we don鈥檛 see much of LRRC15, but then in COVID-19 lungs, we see much more of the protein,鈥� Loo said.

鈥淲e think this newly identified protein could be part of our body鈥檚 natural response to combating the infection creating a barrier that physically separates the virus from our lung cells most sensitive to COVID-19.鈥�

Implications of the research

鈥淲hen 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,鈥� Waller said.

鈥淪ince this receptor can block COVID-19 infection, and at the same time activate our body鈥檚 antivirus response, and suppress our body鈥檚 fibrosis response, this is a really important new gene,鈥� Neely said.

鈥淭his 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.

The authors said they are developing two strategies against COVID-19 using LRRC15 that could work across multiple variants 鈥� 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.

鈥淎 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,鈥� Loo said. 鈥淚f you have less of this protein, you likely have serious COVID. If you have more of it, your COVID is less severe.

鈥淲e are now trying to understand exactly why this is the case.鈥�

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