The Global Pandemic caused by the SARS-CoV2 virus has hit the human civilisation gravely. While we are realising the impact of humans on nature, we also have to accept the fact that we need more scientific advancement. The fact that science has been neglected these years has surfaced with the incapability of scientists and researchers to come up with a vaccine and/or medicine for COVID-19. Disulfiram is showing potential as a medicine against COVID-19.
Waiting For A Long Time
Human coronaviruses were discovered in the 1960s. But none of the previous infections by the virus was as deadly as this one.
The difficulty in making the vaccine/medicine for COVID-19 is because of the characteristics of the virus itself. There are various genera of Coronavirus, including alpha, beta, gamma and delta coronaviruses. The genus which is currently affecting a huge proportion of the world is the Betacoronavirus. However, there are various strains of this betacoronavirus and the vaccine/medicine would be ineffective for another strain.
The deadly coronavirus affects the victim rapidly because it has RNA as its genome. Also, the RNA is both methylated and capped. Due to this, the SARS-CoV- 2 virus is directly translated and there is no need for transcription.
We Need A Solution
Keeping in mind the number of people affected and the number of people who died due to COVID-19, the need of the hour is a vaccine/medicine. The key is to switch off the replication of the enzyme vital for the virus and stop its replication. Presently, this has been achieved by two drugs, one of them is effective against alcoholism and the other against cancer.
The enzyme vital for the virus replication is Mpro(protease) and the two drugs which are also effective against alcoholism and breast cancer are disulfiram and neratinib, respectively.
The research has been carried out by a team of chemists from HSE University and Zelinsky Institute of Organic Chemistry.
Is The Medicine (Disulfiram) Able To Fight Corona Virus?
Drugs or medicines can be assessed against a particular disease/infection by computer remodelling. The same in silico approach has been applied to test the potential of disulfiram against COVID-19. This ‘in silico model’ uses numerical models to test various medicines and determine their potential effectiveness and mechanism of action.
As mentioned earlier, there are several strains of SARS-CoV-2. For example, in Russia itself there are nine unique strains of coronavirus and none of these is present in any other countries. Medicine against one strain is ineffective against any other strain.
FDA approved potential drugs were taken from database and algorithms were used for modelling. Although there are various sulphur-containing drugs showing unusually high ligand binding efficiency at the active site of enzyme Mpro, yet only disulfiram 4 retains stable interactions.
Disulfiram inhibits acetaldehyde dehydrogenase enzyme due to which it is commonly effective for treating alcoholism. This inhibition results in ethanol being converted into acetaldehyde in the body. The increasing acetaldehyde concentration in the body leads to various effects, such as acute intoxication, vomiting, pain and sickness. The alcohol addict thus a conditioned reflex of disgust to alcohol and this helps to overcome alcohol addiction.
Disulfiram is a covalent inhibitor of Mpro protease and helps to inhibit the replication of the virus. Additionally, disulfiram fights against the significant decrease in reduced glutathione, the deficiency of which may lead to several symptoms. The mechanism behind this inhibition is a thiol-disulfide exchange reaction.
Similarly, neratinib inhibits the SARS-CoV-2 replication by inhibiting tyrosinase kinase irreversibly.
Advancement In Science
The research on the effectiveness of disulfiram was carried out by both Chinese biochemists and Russian chemists. China completed the research two weeks earlier than Russia. This was due to powerful computational resources for modelling and capabilities for biological experiments.
The approach for the research is ‘on-top docking’ and it consists of three stages at least. The three stages are namely, modelling, synthesis of potentially active structures and pharmaceutical testing of necessary activity.
Due to the world has to face a deadly virus, the perspectives of people have changed. The scientists, who are usually in the background always have come to the front. We have now realised the importance of science & research. And the investment on research should surely increase after this pandemic.
Reference: “Computational identification of disulfiram and neratinib as putative SARS-CoV-2 main protease inhibitors” by Victor S. Stroylova and Igor V.Svitanko, 4 August 2020, Mendeleev Communications.
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