A widely available drug, used for treatment of asthma and allergies, can also block a protein that is key to replication of SARS-CoV-2, the virus that causes Covid-19, a study by Indian Institute of Science (IISc) researchers has found. The study has been published in the journal eLife.

The drug: The drug, montelukast, is an oral treatment given to prevent wheezing, difficulty breathing, chest tightness, and coughing caused by asthma, and also used to prevent breathing difficulties during exercise, according to the US National Library of Medicine.
“Montelukast is prescribed in India by physicians. It is readily available as tablets and syrup (for kids) in pharmacy shops under different brand names,” IISc Assistant Professor Tanweer Hussain, senior author of the study, told The Indian Express.

In fact, some clinicians were using montelukast to treat Covid-19 patients because of its known role in making breathing easier in asthma patients, Hussain said. “However, it was not known that this drug also has antiviral activity, which we have figured out in this study.”

Antiviral activity: When it infects the human cell, the coronavirus releases a protein called Nsp1, which is key to its replication. The viral protein binds to the host cell’s protein-making machinery, called the ribosome. “If the ribosome is blocked, then the host cell is unable to synthesise proteins needed to fight the viral infection. This helps in the establishment of viral infection,” Hussain said.

Targeting Nsp1, therefore, can reduce the damage inflicted by the virus. And the IISc researchers found that montelukast binds strongly to Nsp1, blocking its access to the ribosome.

Other viral proteins could, of course, still bind elsewhere on the host cell. “However, blocking viral Nsp1 allows the host cells to synthesise immune effector proteins to fight the viral infection,” Hussain said.

Also, Nsp1’s mutation rate is very low compared to other viral proteins, which means Nsp1 is likely to remain largely unchanged in any virus variants that emerge, Hussain said. Hence drugs targeting this region are expected to work against all such variants.

How the drug was identified: The researchers first used computational modelling to screen more than 1,600 drugs approved by the US Food and Drug Administration (FDA). “A new molecule will have to clear all phase trials before it can be prescribed to patients, which would require months and years to complete. Hence we looked for candidates among USFDA-approved drugs,” Hussain said.

The researchers shortlisted a dozen drugs that binds to Nsp1, among which they zeroed in on montelukast and saquinavir, an anti-HIV drug. Lab tests on cultured human cells then showed that only montelukast was able to rescue Nsp1’s inhibition of protein synthesis.

Study: ‘Drug targeting Nsp1-ribosomal complex shows antiviral activity against SARS-CoV-2’, Mohammad Afsar et al, eLife. elifesciences.org/articles/74877

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