Scientists discover protein that stops COVID-19 infection

Scientists have discovered a protein in the lungs that blocks SARS-CoV-2 infection and forms a natural protective barrier in the human body. (Source: Creative Commons)

Scientists at the University of Sydney have discovered a protein in the lungs that blocks SARS-CoV-2 infection and forms a natural protective barrier in the human body.

This leucine-rich repeat containing protein 15 (LRRC15) is an embedded receptor that binds the SARS-CoV-2 virus without transmitting infection.

The study opens up an entirely new area of ​​immunological research around LRRC15 and offers a promising avenue for developing new drugs to prevent viral infection from coronaviruses such as COVID-19 or treat fibrosis in the lungs.

The study is published in the journal PLOS Biology. It was led by Prof. Greg Neely with his team members Dr. Liping Lu, PhD researcher, and graduate student Matthew Waller of the Charles Perkins Center and School of Life and Environmental Sciences.

Immunofluorescent staining shows expression of the novel SARS-CoV-2 spike receptor LRRC15 (green) in a post-mortem section of lung tissue from a person with COVID-19. (CREDIT: University of Sydney)

The university study is one of three independent papers that reveal the interaction of this specific protein with COVID-19.

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“Together with two other groups, one at Oxford and one at Brown and Yale in the US, we have discovered a new receptor on the LRRC15 protein that can stop SARS-CoV-2. We found that this new receptor acts by binding to the virus and isolating it, which reduces the infection,” said Professor Neely.

“For me, as an immunologist, the fact that there is a natural immune receptor that we did not know about that lines our lungs and blocks and controls the virus is insanely interesting.

“Now we can use this new receptor to develop broad-spectrum drugs that can block viral infection or even suppress pulmonary 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 mainly uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, so the COVID-19 virus often causes serious problems in this organ of infected people.

Like ACE2, LRRC15 is a coronavirus receptor, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. However, it can stick to the virus and immobilize it. In doing so, it prevents infection of other vulnerable cells.

“We think it acts like a velcro, a molecular velcro, in the sense that it attaches to the spike of the virus and then pulls it away from the target cell types,” Dr. Lu said.

“Essentially the virus is covered by another part of the Velcro, and as long as it tries to get to the main receptor, it can get into that LRRC15 mesh,” Waller said.

LRRC15 is present in many locations such as the lungs, skin, tongue, fibroblasts, placenta, and lymph nodes. But researchers have found that human lungs catch fire with LRRC15 after infection.

“When we stain the lungs of healthy tissue, we don’t see a lot of LRRC15, but then we see a lot more protein in the COVID-19 lungs,” Dr. Lu said.

“We think this newly identified protein may be part of our body’s natural response to fight infection by creating a barrier that physically separates the virus from the cells in our lungs that are most susceptible to COVID-19.”

Research implications

“When we looked at how this new receptor works, we found that this receptor also controls antiviral responses as well as fibrosis and can link COVID-19 infection to pulmonary fibrosis that occurs during long-term COVID,” Waller said. .

“Because this receptor can block COVID-19 infection and at the same time activate our body’s antiviral response and suppress our body’s response to fibrosis, this is a really important new gene,” said Professor Neely.

“This discovery could help us develop new antiviral and antifibrotic drugs to treat pathogenic coronaviruses and possibly other viruses or other situations where pulmonary fibrosis occurs.

“There are no good cures for fibrosis: for example, idiopathic pulmonary fibrosis is currently untreatable.”

Fibrosis is a condition in which lung tissue becomes scarred and thickened, causing difficulty in breathing. 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 in several ways: one that targets the nose as a preventive treatment and one that targets the lungs in severe cases.

The researchers also said the presence or absence of LRRC15, which is involved in lung repair, is an important indicator of how severe a COVID-19 infection can become.

“A group from Imperial College London independently found that the absence of LRRC15 in the blood is associated with more severe COVID, confirming what we think.” Dr. Lu said. “If you have less of this protein, you probably have serious COVID. If you have more, your COVID is less severe.

“Now we are trying to understand exactly why this is so.”

The study included screening human cell cultures for the presence of genes and examining the lungs of patients with COVID-19.

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Note: Materials provided above by the University of Sydney. Content can be edited for style and length.

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