Chemists from HSE University and the Zelinsky Institute of Organic Chemistry have discovered that disulfiram, a drug used to treat alcoholism, and neratinib, a potential breast cancer drug, can be used to fight COVID-19, the infection caused by the novel coronavirus.
The findings were published in the journal of Mendeleev Communications.
The Russian chemists explained that the conservative proteins of the virus, such as the main protease (M-pro), play a great role in coronavirus replications so it is important to inhibit its function in order to slow down or completely stop the production of the virus in the body.
Study author Igor Svitanko said, “We decided not to focus on the previously described active site, but to investigate the whole surface of M proprotein with many medications, hoping that the big calculation powers would return useful ‘dockings.’”
The potential drugs that can target this protein were taken from the database of drugs approved by the US Food and Drug Administration (FDA).
The researchers demonstrated that disulfiram retained stable interactions. Currently, disulfiram is commonly used for treating alcoholism.
Apart from disulfiram, the team was the first to predict the potential efficiency of an experimental breast cancer drug called neratinib against COVID-19. In 2017, the FDA approved neratinib as an adjuvant treatment of breast cancer.
The scientists have shown that both drugs have the potential to inhibit M-pro. Disulfiram can probably block the M-pro enzymatic activity, while neratinib binding suggests the possibility of covalent interaction.
The study of the two drugs was performed in July at Reaction Biology Corp., a certified lab in the U.S.
The study demonstrated that disulfiram inhibits M-pro in 100 nm concentration, while neratinib demonstrated activity on M-pro but it was not sufficient for clinical use.
The main achievement is the demonstration that the ‘on-top docking’ approach is working and returns quite realistic and controllable results. The team is planning to include molecular modeling of drugs for diseases that have demonstrated safety and efficacy.
