MOSCOW – The drug disulfiram is a common treatment for alcoholism due to its ability to produce a number of unpleasant effects after drinking. From headaches, to nausea, to sweating, it works by essentially causing an immediate hangover. Now, Russian chemists suggest that disulfiram may also be useful in treating COVID-19.
Researchers in Moscow say molecular modeling is focusing on identifying structural components in SARS-CoV-2, the virus responsible for COVID-19. The work is looking for areas that can be targeted to slow down or stop virus from replicating.
The study reveals that disulfiram and another drug, neratinib, have a special ability to lock on and possibly deactivate SARS-CoV-2.
Finding COVID-19’s weak spot
The Russian team also focuses on SARS-CoV-2 components that are resistant to mutation. Mutation resistance is important in antiviral drug development because viruses commonly adapt to antibiotics. If an antiviral drug targets a viral component that is prone to mutation, then the drug may not work once the virus mutates.
A key SARS-CoV-2 enzyme called M pro plays a pivotal role in controlling viral replication and is also mutation resistant. This makes it an excellent candidate target for COVID-19 drugs. However, blocking M pro is not easy.
In many cases, antiviral drugs bind or “dock” to specific components of a virus known as “active sites.” Researchers say normal docking doesn’t work for SARS-CoV-2. To resolve this dilemma, the chemists used a technique they developed shortly before the pandemic began, known as “on-top docking.”
“We decided not to focus on the previously described active site, but to investigate the whole surface of M pro protein with many medications, hoping that the big calculation powers would return useful ‘dockings,'” says HSE University’s Igor Svitanko in a media release.
Disulfiram shows strongest potential
Using their model of SARS-CoV-2, the researchers were able to screen a huge database of FDA-approved medications to see which ones might be able to dock to M pro and deactivate it. Their search reveals sulfur-containing drugs, such as disulfiram, are able to lock on to the active site of M pro very well. The team adds that neratinib, an experimental breast cancer drug, shows the same ability.
Once the two drugs were identified, scientists Reaction Biology Corp. in the United States set to work validating the modeling data. These experiments demonstrate that disulfiram successfully inhibits M pro. Although the experiments find that neratinib also acts on M pro, its impact is not strong enough for it to have any clinical potential.
In the future, the research team plans to use their molecular modeling approach to identify potential treatments for other diseases.
The study is published in the journal Mendeleev Communications.