Investigators Identify Compound That May Halt Infections, Including Common Cold, COVID-19

Investigators at Canada’s University of British Columbia’s (UBC) Life Science Institute have identified a compound that shows early promise at halting infections, including the common cold and all variants of SARS-CoV-2.

The findings, which have been published in Molecular Biomedicine, show a potential path toward antiviral treatments that could be used against many different pathogens.

“Beyond COVID-19, there are many different types of coronaviruses that can cause serious and sometimes fatal disease, and even more are likely to emerge in the future,” Yossef Av-Gay, MD, an infectious disease professor in UBC’s faculty of medicine and the study’s senior author, said in a statement.

“We’re working toward treatments that can be broadly effective against all types of coronaviruses so that we can respond to not only current health challenges, but also future pandemic threats,” Av-Gay said. “Identifying this compound and the pathway by which it works to stop viruses is an important step in that direction.”

Investigators credit the compound’s broad effectiveness to the unique way it works. The compound targets a human cellular process that coronaviruses use to replicate.

Because viruses cannot reproduce on their own, they rely on protein-synthesis pathways in host cells to create copies. In the case of coronaviruses, they use a human enzyme called GSK3 beta that exists in all human cells.

“We found that coronaviruses hijack this human enzyme and use it to edit the protein that packs its genetic material,” Tirosh Shapira, MD, a postdoctoral fellow at UBC’s faculty of medicine and the study’s first author, said in a statement. “This compound blocks GSK3 beta, which in turn, stops the virus from reproducing and maturing its proteins.”

The compound is part of a broader family of experimental drugs known as GSK3 inhibitors. Since the late 1990s, scientists across academia and industry have been studying GSK3 inhibitors for their potential as treatments for diseases, such as Alzheimer disease, cancer, and diabetes.

“By targeting this cellular pathway, rather than the virus itself, we see broad activity against multiple pathogens. We’re also acting on a pathway that is so far immune to changes between variants and different coronaviruses,” Shapira said.

To identify the compound, investigators screened a library of nearly 100 known GSK3 inhibitors, provided through a collaboration between Takeda Pharmaceutical Company of Japan and UBC. The compounds were tested in cell and tissue models infected with the common cold virus and SARS-CoV-2.

The testing yielded multiple GSK3 inhibitors that showed a high level of effectiveness against the coronaviruses and low toxicity to human cells. The leading compound, identified as T-1686568, inhibited both the common cold virus and SARS-CoV-2.

“While these are early days, it’s encouraging to see broad levels of effectiveness in tissue models,” Shapira said. “Because these compounds require many years of testing and regulatory approval before they can potentially reach patients, we need to be thinking about long-term applications and how this could apply broadly to future viruses and variants.”

Reference
From COVID-19 to the common cold: UBC scientists identify broadly-effective, infection-halting compound. EurekAlert. December 14, 2022. Accessed December 14, 2022. https://www.eurekalert.org/news-releases/974362