A drug to reduce Covid infection by 99%

Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University

All over the world research is currently focused on the development of a drug that might help cure COVID19. At the moment we do not have any treatment for COVID19. Vaccines are the only way the chain of transmission can be broken. Throughout the pandemic, various drugs were proposed for the treatment but trial results showed that they were not efficient. Our knowledge of the virus, its metabolic processes, its mechanism to evade host immunity, and many such aspects have become known with increased research. 4 widely available drugs were tested. One of these drugs reduced the formation of SARS-CoV-2 particles by more than 99%!

How does it work?

A virus after infection enters the host cell to multiply itself. It lacks its replication machinery so it exploits the replication machinery of the host cell and uses the molecular building blocks present in the host cell to develop new virions. When inside the host cell it has to avoid detection by the host’s immune system. To do so they manipulate various metabolic processes in the host cell. Researchers at the German Center for Infection Research (DZIF) and the University of Bonn investigated how SARS-CoV-2 reprograms host cells to gain an overall advantage. They found that the new coronavirus slows down autophagy.

Autophagy is a powerful evolutionarily conserved degradative process that cells use to maintain their health. It also facilitates the capture and clearance of pathogens by the immune system. The researchers analyzed SARS-CoV-2 infected cells and the lung tissue of COVID 19 patients. “SARS-CoV-2 deceives the cell by simulating nutrient-rich status, thereby slowing cellular recycling,” said Dr Gassen, the first author. All viruses are subject to autophagic disposal. The virus likely does this to avoid autophagy. As a result of this finding, the autophagic process was considered a likely target for COVID therapy. 4 drugs that are effective in targeting autophagy were tested. Most importantly, all four drugs are already in use in humans.

What did they find?

The first drug tested was spermidine-a polyamine, which is known to enhance autophagy in humans. It is produced in all human cells and the gut by bacteria. Naturally found in wheat germ, soy, mushroom, and mature cheese it is also widely available as a food supplement. When spermidine was added to cells infected with COVID19, an 85% reduction was observed in the number of viruses produced. Similar results were also shown by spermine- the second drug to be tested. Spermine is another polyamine, a derivative of spermidine that is naturally found in the body. It was found to reduce viral replication by 90%. Substances that occur naturally in humans are less likely to induce side effects. But a downside of this drug is that it has to be used at higher concentrations to show effect. Another downside is that viruses are also known to use polyamine to boost replication. The correct dosage, therefore, becomes crucial and self-medication is strongly advised against.

The third drug was MK-2206- an experimental cancer drug which reduced the production of SARS-CoV-2 infection by approximately 90%. It was therefore found to be a good candidate as a COVID drug. However, the most pronounced antiviral effect was shown by the fourth drug: niclosamide. It has proven to be effective against MERS. Now the study shows niclosamide is also effective against SARS and reduced the production of the virus particle by more than 99%. The drug has already been licensed for use against tapeworm infection in humans for a very long time. Out of the four drugs, niclosamide is the most promising one according to the researchers.

What next?

Niclosamide is currently under phase II clinical trial to test its safety, tolerability, and efficacy combined with camostat (another licensed drug) in patients who have recently been diagnosed with COVID.

Also read: A view into the computational techniques for scRNA-seq

Reference:

1. Gassen, N.C., Papies, J., Bajaj, T. et al. SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. Nat Commun 12, 3818 (2021). https://doi.org/10.1038/s41467-021-24007-w

We at BioXone do not promote the use or consumption of any drug. The article is a summarized report of a published research paper in a reputed journal, as cited above.

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