A team of scientists led by the University of Sydney has recently discovered a protein in the human lungs that blocks Covid-19 infection and thus acts as a natural protective barrier in the organism. The leucine-rich repeat-containing protein 15 (LRRC15) is an inbuilt receptor which binds to the coronavirus without passing the infection. This discovery could open new pathways for developing drugs to prevent infection or even help curing fibrosis in the lungs.
“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,” said study senior author Gregory Neely, a professor of Functional Genomics at Sydney.
“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.”
SARS-CoV-2 infects humans by using a spike protein that binds to a specific receptor in our cells called the angiotensin-converting enzyme 2 (ACE2). Since human lungs have high levels of ACE2 receptor, the virus often causes severe problems in this organ. Although, like ACE2, LRRC15 is also a receptor for the coronavirus, it does not help propagating infection, but rather sticks to the virus and immobilizes it, while preventing 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,” explained study lead author Lipin Loo, a postdoctoral fellow in RNA Therapies at Sydney.
“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,” added co-author Matthew Waller, a PhD student at the same university.
While LRRC15 is present in many areas of the body, including lungs, skin, placenta, fibroblasts, and lymph nodes, the experts found that, after infection with SARS-CoV-2, the lungs light up with such receptors.
“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,” Loo said. “We think this newly identified protein could be part of our body’s natural response to combating the infection by creating a barrier that physically separates the virus from our lung cells most sensitive to Covid-19.”
“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. 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,” Neely concluded.
The study is published in the journal PLoS Biology.
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