Ebselen is a chemical compound with antiviral, anti-inflammatory, anti-oxidant, bactericidal and cell-protective properties.
Using cutting-edge computer simulations, scientists have identified a pre-existing drug, used to treat several diseases, including bipolar disorder and hearing loss, that could prevent the novel coronavirus from replicating in host cells, a breakthrough which could lead to a therapeutic solution against COVID-19.
The study, published in the journal Scientific advances, evaluated the main protease molecule, Mpro, of the new coronavirus which is a key enzyme playing a central role in its life cycle.
According to researchers, including those at the University of Chicago in the United States, Mpro facilitates the virus’s ability to make proteins from its genetic material – RNA – and allows the pathogen to replicate in the host cell. .
Using their expertise in modeling biological molecules, scientists quickly screened thousands of existing compounds for potential use against the virus.
“Due to the large number of compounds considered in high-throughput screens, these calculations must necessarily involve a number of simplifications, and the results must then be evaluated using more refined experiments and calculations,” explained study co-author Juan de Pablo of the University of Chicago.
They discovered that the promising pharmaceutical drug as a weapon against Mpro is Ebselen – a chemical compound with antiviral, anti-inflammatory, anti-oxidant, bactericidal and cell-protective properties.
According to the researchers, Ebselen is used to treat several illnesses, including bipolar disorder and hearing loss.
They said several clinical trials have proven its safety in humans.
In the research, de Pablo and his team developed detailed models of the enzyme and the drug, and with sophisticated supercomputer simulations, they found that Ebselen is able to decrease Mpro activity in two different ways.
“In addition to binding to the catalytic site of the enzyme, Ebselen also binds strongly to a distant site, which interferes with the catalytic function of the enzyme by relying on a mechanism in which information is transported from ‘one region of a large molecule to another remote region. away from it by subtle structural reorganizations, ”said de Pablo.
Scientists say this finding is particularly important because it helps explain the potential effectiveness of Ebselen as a reused drug and reveals a new vulnerability in the virus that was previously unknown and could be useful in development. new therapeutic strategies against COVID-19.
While researchers believe more studies are needed to test the drug against COVID-19, they believe the two binding sites on Mpro show promise for Ebselen as a new drug. “The main protease is one of many proteins in the virus that could be targeted with existing and reused drugs, and there are thousands of compounds to consider,” said de Pablo.
“We are systematically studying each of the proteins involved in the function of the virus and studying their vulnerabilities and their responses to a wide range of drugs,” he added.
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