An international collaboration between American, German, and Swiss scientists has uncovered a protein created by the human immune system that’s capable of strongly impairing various coronaviruses. Most importantly, the researchers say this protein (LY6E) can even inhibit SARS-CoV-2, the coronavirus strain responsible for the COVID-19 global pandemic.
The LY6E protein appears to stop coronaviruses from infecting and fusing with new host cells.
“This finding might lead to the development of new therapeutic approaches against coronaviruses,” comments lead study author Stephanie Pfänder, a professor in the Department for Molecular and Medical Virology at Ruhr-Universität Bochum, in a press release.
Interestingly, the LY6E protein seems to have different effects on various viruses and pathogens. A duo of US researchers, professor John Schoggins and professor Charles Rice, discovered that LY6E actually strengthens the infectious capabilities of the influenza virus. Conversely, however, the LY6E protein has the opposite effect on coronaviruses; neutralizing their infectivity.
Long before COVID-19 appeared, professor Pfänder, who at the time was working and living in Switzerland, traveled to New York in 2017 to visit Charles Rice’s lab at Rockefeller University. Back then, the purpose of that trip was to find and identify any genes that impede or stop coronavirus infections.
“This led to the discovery that LY6E has the opposite effect on coronaviruses compared to influenza viruses,” professor Pfänder remembers.
When Rice and Pfänder investigated further, they discovered that LY6E impedes infectious activity in each coronavirus strain they analyzed (SARS, MERS, and SARS-CoV-2).
How is LY6E achieving this antiviral accomplishment? Cell culture tests performed by the research team showed that LY6E actively interferes with coronaviruses’ abilities to “fuse” with, or infect, new host cells.
“If the virus is unable to fuse with these cells, it can’t cause infection,” explains co-study author Volker Thiel, a professor at the University of Bern.
More evidence of the protein’s effectiveness against coronaviruses was discovered using mouse models. These experiments, which took place at the Southwestern Medical Center of the University of Texas, discovered that the mouse variant of the protein (Ly6e) is essential when it comes to protecting mouse immune cells from infections. Without Ly6e, various immune cells (B-cells, dendritic cells) in a mouse’s body see their overall numbers dwindle, and the cells that remain are weakened and much more vulnerable to infection. Mice with a Ly6e deficiency often pass away from coronavirus infections that should be non-lethal.
Now, it’s important to note that the mouse coronavirus used in the animal models is quite different from SARS-CoV-2. While SARS-CoV-2 usually results in respiratory symptoms, the mouse coronavirus causes hepatitis. Still, observations made using that mouse coronavirus strain are universally accepted by the medical community as an accurate indicator of how coronaviruses replicate, infect, and interact with immune systems in living beings.
“Our study provides new insights into how important these antiviral genes are for the control of viral infection and for an adequate immune response against the virus,” the study’s authors write. “Since LY6E is a naturally occurring human protein, we hope that this knowledge will aid the development of therapies that may one day be used to treat coronavirus infections.”
The full study can be found here, published in Nature Microbiology.