More than six months into the global Coronavirus pandemic, Russian researchers have found that a medication used to treat alcoholism, disulfiram, may help fight the novel Coronavirus or COVID-19, which killed over 715,000 people globally.
Researchers at Russia's National Research University Higher School of Economics (HSE) and Zelinsky Institute of Organic Chemistry have conducted a study which suggested that experts should focus on the structural elements of the novel Coronavirus, which are less subject to mutation during its evolution for the potential treatment. "If we fail to do so, then effective medicines against one strain of the Coronavirus may not be effective after the mutation of the virus," they insist.
As per the findings of the research, published in the journal Mendeleev Communications, the best candidates for this are conservative proteins, such as the enzyme, Mpro that the novel Coronavirus needs to make copies of itself inside the host cell.
Medicine to Fight SARS-CoV-2
Mpro is a protease and also resistant to mutations. As it plays a key role in Coronavirus replication which implies that its inhibition is capable of slowing down or stop its reproduction process inside the body, said the researchers.
While trying to find an effective drug for COVID-19, researchers had looked into the database of medications approved by the U.S. Food and Drug Administration (FDA). The modeling data showed that drugs that contain Sulphur show unusually high ligand efficiency at the active center of Coronavirus main protease Mpro. But researchers also understood that only disulfiram makes stable complexes and acts in two different ways.
First is, disulfiram acts as a covalent inhibitor of the Mpro enzyme as shown previously with other Coronaviruses (MERS and SARS) that bind to the target enzyme and keep it from functioning. Secondly, it works against the decrease of glutathione—an antioxidant—in patients with SARS-CoV-2.
However, the Russian scientists have also claimed that they are the first to predict the potential efficiency of a tyrosine kinase inhibitor anticancer drug, neratinib, against SARS-CoV-2. The drug is used as an adjuvant in the treatment of breast cancer.
But as per the researchers, in terms of novel Coronavirus, neratinib and disulfiram act differently. A statement by HSE University suggested that disulfiram can inhibit Mpro at a concentration of 100 nanomolar but the effect of second substance—neratinib—is insufficient for clinical use.
