A research team at the Pritzker School of Molecular Engineering (PME) at the University of Chicago used computer simulations to identify a preexisting drug that could be utilized as a potential therapeutic against SARS-CoV-2. Their findings are published in the journal, Science Advances. Professor Juan de Pablo and his students used molecular modeling to find a treatment against COVID-19.
"By virtue of the large number of compounds considered in high throughput screens, those calculations must necessarily involve a number of simplifications, and the results must then be evaluated using experiments and more refined calculations," de Pablo explained.
The research team focused on the SARS-CoV-2 vulnerabilites while identifying therapeutic options. They chose its main protease, Mpro, which is a key coronavirus enzyme that plays a central role in the virus' life cycle. It gives the virus the ability to transcribe its RNA and replicate its genome within the host cell.
A pharmaceutical drug that shows promise as a weapon against Mpro is Ebselen. Ebselen is a chemical compound with anti-viral, anti-inflammatory, anti-oxidative, bactericidal, and cell-protective properties. Ebselen is currently used as a therapeutic to multiple issues including bipolar disorders and hearing loss. When used with silver, Ebselen treats five antibiotic-resistant Gram-negative bacteria and has already had several clinical trials proven its safety for human use.
"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 reorganizations," de Pablo says.