Asthma drug blocks protein crucial to replication of coronavirus: IISc study

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Last Updated28/04/2022

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.

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The drug, montelukast, is an oral treatment given to prevent wheezing, difficulty breathing, chest tightness, and coughing caused by asthma.
It 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.
Some clinicians were using montelukast to treat Covid-19 patients because of its known role in making breathing easier in asthma patients.
It was not known that this drug also has antiviral activity, which has been figured out in this study.

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 synthesize proteins needed to fight the viral infection.
This helps in the establishment of viral infection.
Targeting Nsp1 can reduce the damage inflicted by the virus.
The IISc researchers found that montelukast binds strongly to Nsp1, blocking its access to the ribosome.
Blocking viral Nsp1 allows the host cells to synthesize immune effector proteins to fight the viral infection.

The researchers first used computational modeling 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.
Proper prescription would require months and years to complete.
Hence researchers looked for candidates among USFDA-approved drugs.
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.

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