Finding may lead to key solution against Covid-19  

A pre-existing drug Ebselen, used to treat multiple diseases, including bipolar disorders and hearing loss could prevent the coronavirus from replicating in host cells, a scientific advance that may lead to a therapeutic solution against Covid-19.

Ebselen is a chemical compound with anti-viral, anti-inflammatory, anti-oxidative, bactericidal, and cell-protective properties.

The study, published in the journal Science Advances, assessed the molecule main protease, Mpro, of the novel coronavirus which is a key enzyme that plays a central role in its life cycle. The study is conducted by using state-of-the-art computer simulations.

According to the researchers, including those from the University of Chicago in the US, Mpro facilitates the virus’ ability to make proteins from its genetic material — RNA — and enables the pathogen to replicate within the host cell.

Using their expertise in modeling biological molecules, the scientists rapidly screened thousands of existing compounds for potential use against the virus.

“By the 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” explained study co-author Juan de Pablo from the University of Chicago.

In combination with silver, Ebselen treats five clinically difficult-to-manage antibiotic-resistant Gram-negative bacteria. Several clinical trials have proven its safety for use in humans.

Juan de Pablo and his students 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,” de Pablo said.

The finding is 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 and that could be useful in developing new therapeutic strategies against Covid-19, according to reports.