AUSTRALIA — University of Sydney scientists have discovered a protein in the lung that blocks SARS-CoV-2 infection and forms a natural protective barrier in the human body.
The leucine-rich repeat-containing protein 15 (LRRC15) also forms a natural protective barrier in the body of human beings.
It is an inbuilt receptor that attaches to the SARS-CoV-2 virus and drags it away from the target cells.
Additionally, their research discovered that LRRC15 is expressed in fibroblast cells, which play a crucial role in regulating lung fibrosis – a condition characterized by the formation of damaged and scarred lung tissue.
As Covid-19 can result in lung fibrosis, this finding could potentially have important implications for individuals experiencing long-term effects of the virus, to offer a pathway for developing new drugs for preventing infection from coronaviruses such as Covid-19 or dealing with lung fibrosis
Published in the PLOS Biology journal, the study was led by Professor Greg Neely along with postdoctoral researcher Dr. Lipin Loo and Ph.D. student Matthew Waller at the Charles Perkins Centre and the School of Life and Environmental Sciences.
Neely said: “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.
“We can now use this new receptor to design broad-acting drugs that can block viral infection or even suppress lung fibrosis.”
The researchers used tissue-cultured human cells to search the entire human genome for proteins that can bind to Sars-CoV-2, the virus that causes Covid-19.
This was accomplished using the CRISPR genetic engineering tool, which allowed them to activate all genes in the human genome and then determine which of those genes allow human cells to bind to the Sars-CoV-2 spike protein. The spike protein is required for the virus to infect human cells.
Like Angiotensin-converting enzyme 2 (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 immobilize it. In the process, it prevents other vulnerable cells from becoming infected.
The study authors are developing two Covid-19 strategies with the help of LRRC15 that is expected to work across several variants.
The researchers added that the presence or lack of the protein indicates the severity of Covid-19 infection.
Humans do not have LRRC15 until Sars-CoV-2 enters the body. It appears to be a component of a new immune barrier that protects against serious Covid-19 infection while activating the body’s antiviral response.
Despite those patients who died from Covid-19 producing LRRC15, the researchers believe not enough was produced to be protective, or it was produced too late to help.
“When we look at lungs from patients that died of Covid there is much of this protein,” Neely said. “But we couldn’t look at the lungs of patients that survived Covid as lung biopsy is not something that is easy to do on live people. We predict there is more of this protein in survivors versus those that died of Covid.”
A separate study from London that examined blood samples for LRRC15 found the protein in the blood was lower in patients with severe covid compared to patients that had mild Covid, supporting this theory.
“Our data suggest that higher levels of LRRC15 would result in people having less severe disease,” Neely said.
As part of the study, the researchers screened human cell cultures for genes and investigated Covid-19 patients’ lungs.
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