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COVID-19, the disease caused by the novel coronavirus or SARS-CoV-2, has left researchers around the world puzzled. Many questions about this new disease still remained answered. Meanwhile, different research groups are coming up with new findings and theories almost every day. But none have been able to find the solution to end the pandemic. There is also a competition among the countries to launch the first COVID-19 vaccine. According to the World Health Organisation (WHO), over 160 potential vaccines are under development, out of which about 26 are being tested in humans. Studies are also being done to test the efficacy of several existing drugs (designed for the treatment of other ailments) against the coronavirus infection. In the latest development, a study has suggested disulfiram, the medication used to treat alcoholism, may help in the fight against the novel coronavirus.
In the study, researchers from National Research University Higher School of Economics (HSE) in Russia demonstrated that disulfiram inhibits SARS-CoV-2 main protease Mpro, the protein that plays a major role in coronavirus replication. The study results were published in the Mendeleev Communications journal.
The researchers noted that a potential treatment should target the structural elements of the novel coronavirus that are less subject to mutation during its evolution. Otherwise, they said, a medication effective against one strain would no longer be effective against another. According to them, the best targets for potential coronavirus treatment are conservative proteins, such as the SARS-CoV-2 virus main protease M pro.
M pro is resistant to mutations but plays a major role in the virus replication. This means inhibition of this protein can slow down or even completely stop its reproduction inside the body, the researchers noted.
For their study, they selected potential drugs from the database of medications approved by the US Food and Drug Administration (FDA). The modeling data showed that sulfur-containing drugs have unusually high ligand efficiency at the active centre of SARS-CoV-2 main protease Mpro, but only disulfiram 4 retains stable interactions.
The researcher claimed that disulfiram, the drug most commonly used for treating alcoholism, can fight SARS-CoV-2 in two ways.
The drug is a covalent inhibitor and can fight COVID-19 symptoms such as the significant decrease in glutathione, which is an important antioxidant. Deficiency of glutathione may lead to severe manifestations of the disease, the researchers said.
During tests, the researchers found that disulfiram really inhibits M pro in 100 nm concentration, which confirmed the results of the modeling.
The Russian chemists also tested the efficiency of neratinib, an irreversible tyrosine kinase inhibitor, against SARS-CoV-2. While neratinib demonstrated activity on M pro, it was insufficient for clinical use, they said.
Various drugs are being used for the treatment of coronavirus patients and some have shown positive results. Drugs approved COVID-19 treatment in India include: