Asthma drug montelukast can block COVID-19 from attacking the immune system

BENGALURU, India — A common asthma and allergy drug can also protect people from COVID-19, a new study reveals. Researchers in India have found that montelukast blocks a key protein that COVID-19 uses to attack the human immune system.

The U.S. Food and Drug Administration approved montelukast for use in reducing inflammation due to asthma, hay fever, and hives over 20 years ago. Now, study authors say the drug can bind to one end of the SARS-CoV-2 protein called Nsp1. It’s one of the first viral proteins the virus unleashes after infecting people.

Nsp1 can bind to ribosomes, which is the protein-making machinery inside immune cells. From there, the viral proteins shut down the production of key human proteins the body needs to maintain a healthy immune system. By blocking Nsp1, researchers believe they can reduce the damage COVID-19 inflicts on patients.

“The mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral proteins,” explains senior author Tanweer Hussain, an assistant professor at the Indian Institute of Science (IISc), in a university release.

Importantly, the team believes montelukast will be effective against all of COVID’s variants because Nsp1 remains basically the same even as the virus mutates.

Finding pandemic treatments in repurposed drugs

The study authors searched through more than 1,600 FDA-approved drugs, looking for one that could strongly bind to Nsp1. Out of all of those drugs, the team cut the list to a dozen, including montelukast and saquinavir, an anti-HIV drug.

“The molecular dynamic simulations generate a lot of data, in the range of terabytes, and help to figure out the stability of the drug-bound protein molecule. To analyze these and identify which drugs may work inside the cell was a challenge,” says Mohammad Afsar, a former project scientist at IISc’s Department of Molecular Reproduction, Development and Genetics.

Hussain’s team cultured human cells in a lab that specifically produce Nsp1. They then treated the cells with montelukast and saquinavir separately. Results show montelukast was the only drug that could successfully inhibit protein synthesis by Nsp1.

Afsar explains that montelukast not only binds to the viral protein strongly, but it also stays bound to Nsp1 long enough to keep the virus from damaging host cells.

montelukast
Targeting Nsp1 with montelukast helps prevent shutdown of host protein synthesis (Credit: Mohammad Afsar)

Montelukast shows success against the real virus

Researchers later tested montelukast on live virus samples in a Bio-Safety Level 3 facility. Those tests found that the drug reduces viral loads of SARS-CoV-2 in infected cells.

“Clinicians have tried using the drug… and there are reports that said that montelukast reduced hospitalization in COVID-19 patients,” says Hussain.

The team is now planning to see if they can modify montelukast to make it more potent against COVID-19. They are also continuing to look for other available drugs which may have the ability to treat COVID patients.

The study is published in the journal eLife.

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