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Even after more than half a year, there are still a lot of unanswered questions about the Sars-Cov-2 virus, which causes the disease COVID-19. Although we now know to a large extent how it spreads and what it can do in the body, it remains a mystery. Yet how to prevent the virus from spreading in the body in the first place is something that scientists all over the world are working on at full speed. An international team from Germany, Switzerland, and the USA has now taken a big step towards finding the answer to this problem.

The scientists have been able to prove that the LY6E protein, a protein produced by the human immune system that can effectively inhibit coronaviruses, can also prevent Sars-Cov-2 from triggering an infection. ” This provides information on potential treatment strategies,” says Prof. Dr. Stephanie Pfänder from the Department of Molecular and Medical Virology at the Ruhr University Bochum (RUB, Germany), first author of the study ‘LY6E impairs coronavirus fusion and confers immune control of viral disease,’ which the team published in the academic journal Nature Microbiology

Useless against flu, good against coronavirus

The US-American researchers Prof. Dr. John Schoggins and Prof. Dr. Charles Rice discovered some time ago that the LY6E protein plays a role in various diseases and, for example, increases the infectiousness of flu-triggering viruses. Research into genes that inhibit coronaviruses has led to the discovery “that LY6E has the opposite effect on coronaviruses compared to influenza viruses: It has a strong inhibitory effect on them,” Pfänder states.

Further studies have shown “that the protein exerts this inhibitory effect on all tested coronaviruses, including the pathogens of Sars and Mers as well as Sars-Cov-2, the cause of Covid-19”. Tests with different cell cultures have shown that LY6E impairs the ability of the virus to fuse with the body’s host cells. “If the virus is unable to merge with these cells, it is prevented from causing an infection,” explains lead author Prof. Dr. Volker Thiel from the Swiss University of Bern.

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Stephanie Pfänder looks for genes that inhibit coronaviruses. © RUB, Marquard

Evidence in animal models

Experiments at the Southwestern Medical Center of the University of Texas have shown “that the mouse variant of the protein called Ly6e is crucial for protecting immune cells from infection.” Without Ly6e, immune cells such as dendritic cells and B cells would become more susceptible to infection and their numbers would drastically decrease, the researchers report. Mice without Ly6e in their immune cells also turned out to be susceptible to a mouse coronavirus and died from it, even though it is not normally fatal.

The mouse coronavirus used in the experiment differs “significantly” from the Sars-Cov-2 virus and does not cause respiratory disease, but hepatitis instead. Nevertheless, it is still suitable for understanding basic concepts of coronavirus replication and immune responses in living animals.

“Our study sheds new light on how important these antiviral genes are for controlling viral infections and for an effective immune response against the virus,” the authors stress. ” Given that LY6E is a naturally occurring human protein, we hope that this knowledge will help in the development of therapies that may one day be used to treat coronavirus infections.” A therapeutic approach that mimics the mechanism of action of LY6E may provide a first line of defense against novel coronavirus infections.

Stephanie Pfänder was awarded a Marie-Skłodowska Curie Fellowship from the European Commission.