Newswise - Researchers at UBC's Institute for Life Sciences have identified a compound that shows promise in stopping infection from various coronaviruses, including all variants of SARS-CoV-2 and the common cold.
The results, published this week in Molecular Biomedicine, provide a possible route for an antiviral treatment that could be used against many different pathogens.
"Beyond COVID-19, there are many strains of coronaviruses that can cause serious and sometimes fatal illness, and more are likely to emerge in the future," said Dr. Yosef Av-Gey, Professor of Infectious Diseases at the UBC School of Medicine and senior author of the study.
"We are working on treatments that can be broadly effective against all types of coronaviruses so that we can respond not only to current health challenges but also to the threat of future pandemics." Identifying this link, and how to stop the virus, is an important step in this direction.
Target the host, not the virus
Researchers attribute the effectiveness of a wide range of compounds to their unique mode of action. Instead of targeting the virus itself, the compound targets the human cellular processes used by the coronavirus to replicate.
Since viruses cannot reproduce themselves, they depend on protein synthesis pathways in the host cell to make copies of themselves. In the case of the coronavirus, they used a human enzyme called GSK3 beta, which is found in all human cells.
"We found that the coronavirus hijacks this human enzyme and uses it to edit the proteins that package its genetic material," said Dr. Tirosh Shapira, a postdoctoral fellow at the UBC School of Medicine and first author of the study. "This compound blocks GSK3 beta, which in turn stops viral replication and its proteins from maturing."
The compound is part of a large family of experimental drugs known as GSK3 inhibitors. Since the late 1990s, academia and industry scientists have studied GSK3 inhibitors for their potential to treat a variety of diseases, including diabetes, Alzheimer's disease, and cancer.
“By targeting this cellular pathway rather than the virus itself, we are seeing broad activity against many pathogens. We are also working on signaling pathways that are so far immune to changes between different variants and coronaviruses," said Dr. shapira
Future Care
To identify the compound, the research team searched a library containing nearly 100 known GSK3 inhibitors available through a collaboration between UBC and Takeda Pharmaceutical Company in Japan. The compound was tested in cell and tissue models infected with SARS-CoV-2 and the common cold virus.
The tests revealed several GSK3 inhibitors showing high anti-coronavirus potential and low toxicity to human cells. The lead compound, identified as T-1686568, inhibited both SARS-CoV-2 and the common cold virus, a key criterion the authors used in their search for broad-spectrum protection.
"While this is still early days, it is very encouraging to see broad efficacy rates in tissue models," said Dr. shapira “Because these compounds require years of testing and regulatory approval before they can potentially reach patients, we need to think about long-term applications and how this might apply to viruses and variants in the future.”
The research was conducted at UBC FINDER, a level 3 biocontainment facility at UBC, where researchers work with highly infectious pathogens to develop future treatments.
"We're not just fighting SARS-CoV-2, we're looking forward to what comes next," said Dr. shapira “We are focused on identifying future-proofed treatments for variants and viruses that emerge along the way that rely on the same cellular mechanisms for growth and infection.
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