Researchers at UBC’s Life Sciences Institute have identified a compound that shows potential for early thwarting of infections by a variety of coronaviruses, including all variants of SARS-CoV-2 and the common cold.
The findings, published this week in Molecular Biomedicine, reveal potential avenues for antiviral treatments that can be used against many different pathogens.
“Beyond COVID-19, there are many different types of coronaviruses that can cause serious, sometimes fatal illness, and many more may emerge in the future,” said UBC. Yossef Av-Gay, Ph.D., Professor of Infectious Diseases, Faculty of Medicine, said. Senior author in medicine and research.
“We are working on broadly effective treatments against all types of coronaviruses to meet not only current health challenges but also future pandemic threats. , identifying the pathways that work to thwart the virus is an important step in that direction.”
Target the host, not the virus
Researchers attribute the compound’s broad efficacy to its unique behavior. Rather than targeting the virus itself, the compound targets human cellular processes that coronaviruses use to replicate.
Viruses cannot replicate themselves, so they rely on protein synthesis pathways within the host cell to make copies of themselves. For the coronavirus, she uses a human enzyme called GSK3 beta that is present in all human cells.
“We found that the coronavirus hijacks this human enzyme and uses it to edit the proteins that pack its genetic material,” said a postdoctoral fellow in UBC’s School of Medicine and the study’s first author. One Dr. Tirosh Shapira said: “This compound blocks GSK3beta, preventing the virus from replicating and maturing that protein.”
This compound is part of a broader family of experimental drugs known as GSK3 inhibitors. Since the late 1990s, scientists in academia and industry have investigated the potential of his GSK3 inhibitors as treatments for many diseases such as diabetes, Alzheimer’s disease and cancer.
“By targeting this cellular pathway, rather than the virus itself, we see broad activity against multiple pathogens. We do,” says Dr. Shapira.
Promising treatment
To identify this compound, the research team screened a library of approximately 100 known GSK3 inhibitors provided through a collaboration between UBC and Takeda Pharmaceutical Company Limited in Japan. Compounds were tested in cell and tissue models infected with SARS-CoV-2 and cold viruses.
This trial yielded multiple GSK3 inhibitors that showed high levels of efficacy against coronaviruses and low toxicity to human cells. The lead compound, identified as T-1686568, inhibited both SARS-CoV-2 and the common cold virus. This is the main criterion used by the authors in their search for broad spectrum protection.
“We are working to treat all types of coronaviruses so that we are ready not only for current health challenges, but also for future pandemic threats.”
Dr. Joseph av Gay
“We’re just getting started, but it’s encouraging to see broad levels of validity in our organizational model,” says Dr. Shapira. “These compounds require years of testing and regulatory approval before they can potentially reach patients, so long-term applications and how this might affect future viruses and subspecies. We need to think about whether it can be applied broadly.”
This research was conducted at UBC FINDER, UBC’s Level 3 biocontainment facility. Researchers work with highly infectious pathogens to develop future treatments.
“We are not just fighting SARS-CoV-2, we are looking at what comes next,” Dr. Shapira said. “Our focus is on identifying potential therapeutics against mutants and viruses that will emerge and rely on the same cellular mechanisms to grow and infect.”
Original: From COVID-19 to the common cold: UBC scientists identify broadly effective infection-stopping compounds
Than: University of British Columbia
