NEW YORK: Using state-of-the-art computer simulations, the researchers have identified a preexisting drug that could fast-track a solution to this worldwide Covid-19 pandemic.
For the study, published in the journal Science Advances, the research team from the University of Chicago in the US first focused on finding a weakness in the Covid-19 virus to target. They chose its main protease: Mpro. Mpro is a key coronavirus enzyme that plays a central role in the virus’ life cycle. It facilitates the virus’ ability to transcribe its RNA and replicate its genome within the host cell.
The researchers found that the pharmaceutical drug that shows promise as a weapon against Mpro is Ebselen — a chemical compound with anti-viral, anti-inflammatory, anti-oxidative, bactericidal, and cell-protective properties.
Ebselen is used to treat multiple diseases, including bipolar disorders and hearing loss.
Several clinical trials have proven its safety for use in humans. According to the study, the research team set out to develop detailed models of the enzyme and the drug. Using those models and sophisticated supercomputer simulations, they discovered that the small Ebselen molecule is able to decrease Mpro’s activity in two different ways.
“In addition to binding at the catalytic site of the enzyme, Ebselen also binds strongly to a distant site, which interferes with the enzyme’s catalytic function by relying on a mechanism in which information is carried from one region of a large molecule to another region far away from it through subtle structural reorganisations,” said study author Juan de Pablo.
The finding was particularly important because it helped explain Ebselen’s potential efficacy as a repurposed drug, and it revealed a new vulnerability in the virus that was previously not known.
The research team’s discovery of two binding sites looks promising for Ebselen to be a new drug lead for the design and development of new Mpro inhibitors and Covid-19 treatment. The team also noted that much work is yet to be done. “The main protease is one of many proteins in the virus that could be targeted with existing, repurposed drugs, and there are thousands of compounds to be considered,” de Pablo said.
“We are systematically investigating each of the proteins involved in the virus function and investigating their vulnerabilities and their responses to a wide range of drugs,” de Pablo noted.
