New research demonstrates that an existing drug, called Ebselen, has the potential to disrupt SARS-CoV-2. This is the virus responsible for COVID-19.
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The recent study, which appears in the journal Science Advances, could help develop Ebselen as a new treatment for COVID-19. The study also provides clues as to which other existing drugs scientists should prioritize in the hunt for effective therapies.
The sudden emergence and rapid spread of COVID-19 has catalyzed a significant amount of research into possible treatments and therapies.
SARS-CoV-2 bears many similarities to other coronaviruses, such as SARS-CoV, which is responsible for severe acute respiratory syndrome (SARS). However, “repurposing SARS drugs for COVID-19 may not be effective,” according to the authors of the new study.
Treatments and therapies are important, as a vaccine for SARS-CoV-2 — which is the world’s best hope of significantly restricting transmission — could be years away.
Although researchers are moving quickly toward a vaccine, it is important to identify ways to either reduce the severity of COVID-19 or reduce a person’s chance of contracting it.
However, even drug treatments can take many years to develop, and researchers need to carefully vet them to ensure that they are safe for general use.
Unlike vaccines, existing drugs that scientists have already tested and vetted may be ready for use in the clinic much sooner.
Previous research suggests that Ebselen might inhibit enzymes in SARS-CoV-2 that are essential for it to replicate within a host cell. In particular, it inhibits the virus’s main protease, which is known as Mpro.
Like all viruses, SARS-CoV-2 spreads by replication, taking over cells in a host organism. Inhibiting replication gives the immune system a better chance of combating the virus, potentially reducing the duration and severity of COVID-19.
The recent research looked in more detail at Ebselen to better understand whether or not it could be effective against SARS-CoV-2. This is important, as initial studies that identify promising existing drugs depend on simplifications. These simplifications allow scientists to process large databases rapidly, but they can produce errors.
According to corresponding study author Juan de Pablo, a professor in the Pritzker School of Molecular Engineering at the University of Chicago, IL, “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.”
In the past, doctors have used Ebselen to help treat bipolar disorder and hearing loss. Studies have also shown that it has antibacterial and anti-inflammatory properties. As a consequence, scientists have already shown that Ebselen is safe.
To examine Ebselen’s potential as the basis of a treatment for COVID-19, the researchers produced sophisticated computer models of both Ebselen and the main protease, Mpro.
They found that Ebselen was not only likely to be effective at inhibiting the enzyme, but that it might do so in more than one way.
As Prof. de Pablo explains, “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.”
This is good news regarding Ebselen’s potential use against COVID-19, but it also outlines another vulnerability in the virus that scientists might keep in mind as they search for other drug candidates.
Despite this promising work, researchers will need to carry out much more research to determine whether or not Ebselen is effective and to bring it to a point where doctors can use it in practice.
Crucially, the recent study only shows the potential effectiveness of the drug; real-world trials will be necessary to see if the findings hold true outside of the laboratory.
The authors of the study plan to continue their search for SARS-CoV-2’s weak spots.
“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,” says Prof. de Pablo.
“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.”
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