The Indian Institute of Science, Bengaluru scientists have conducted a study that revealed that Montelukast- a drug used for the treatment of Asthama has the potential to stop Covid variants from replicating within the body of the infected.
The study was published in the journal eLife. The study states that “montelukast sodium hydrate can be used as a lead molecule to design potent inhibitors to help combat SARS-CoV-2 infection.” Montelukast, used to reduce inflammation caused by conditions like asthma, hay fever and hives, has been found effective against Covid-19.
The drug has the potential to reduce SARS-CoV-2, the virus that causes Covid-19, from replicating in human immune cells, the study revealed.
Researchers at the IISc found that the drug binds strongly to one end (‘C-terminal’) of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. This protein can bind to ribosomes the protein-making machinery inside our immune cells and shut down the synthesis of vital proteins required by the immune system, thereby weakening it.
Tanweer Hussain, Assistant Professor in the Department of Molecular Reproduction, Development and Genetics (MRDG), IISc, and senior author of the study explains that the mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral protein and since Nsp1 is likely to remain largely unchanged in any variants of the virus that emerge, drugs targeting this region are expected to work against all such variants.
The latest study comes in the backdrop of a major surge in coronavirus cases across the world, including in India, where Omicron remains the dominant variant in the fresh cases.
The researchers screened over 1,600 US Food and Drug Administration (FDA)-approved drugs in order to find the ones that bound strongly to Nsp1 using computational modelling. They then shortlisted a dozen drugs including montelukast and saquinavir, an anti-HIV drug, to understand the stability of the drug-bound protein molecule. The team then cultured human cells in the lab that specifically produced Nsp1 and treated them with montelukast and saquinavir separately.
They found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.
“There are two aspects: one is affinity and the other is stability. The anti-HIV drug (saquinavir) showed good affinity, but not good stability. Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis,” Tanweer Hussain, Assistant Professor in the Department of Molecular Reproduction said in a statement.
The researchers also tested the effect of the drug on live viruses, in the Bio-Safety Level 3 (BSL-3) facility at the Centre for Infectious Disease Research (CIDR). “Clinicians have tried using the drug and there are reports that said that montelukast reduced hospitalisation in COVID-19 patients,” says Hussain, adding that the exact mechanisms by which it works still need to be fully understood.
The Indian Institute of Science, Bengaluru scientists have conducted a study that revealed that Montelukast- a drug used for the treatment of Asthama has the potential to stop Covid variants from replicating within the body of the infected.
The study was published in the journal eLife. The study states that “montelukast sodium hydrate can be used as a lead molecule to design potent inhibitors to help combat SARS-CoV-2 infection.” Montelukast, used to reduce inflammation caused by conditions like asthma, hay fever and hives, has been found effective against Covid-19.
The drug has the potential to reduce SARS-CoV-2, the virus that causes Covid-19, from replicating in human immune cells, the study revealed.
Researchers at the IISc found that the drug binds strongly to one end (‘C-terminal’) of a SARS-CoV-2 protein called Nsp1, which is one of the first viral proteins unleashed inside human cells. This protein can bind to ribosomes the protein-making machinery inside our immune cells and shut down the synthesis of vital proteins required by the immune system, thereby weakening it.
Tanweer Hussain, Assistant Professor in the Department of Molecular Reproduction, Development and Genetics (MRDG), IISc, and senior author of the study explains that the mutation rate in this protein, especially the C-terminal region, is very low compared to the rest of the viral protein and since Nsp1 is likely to remain largely unchanged in any variants of the virus that emerge, drugs targeting this region are expected to work against all such variants.
The latest study comes in the backdrop of a major surge in coronavirus cases across the world, including in India, where Omicron remains the dominant variant in the fresh cases.
The researchers screened over 1,600 US Food and Drug Administration (FDA)-approved drugs in order to find the ones that bound strongly to Nsp1 using computational modelling. They then shortlisted a dozen drugs including montelukast and saquinavir, an anti-HIV drug, to understand the stability of the drug-bound protein molecule. The team then cultured human cells in the lab that specifically produced Nsp1 and treated them with montelukast and saquinavir separately.
They found that only montelukast was able to rescue the inhibition of protein synthesis by Nsp1.
“There are two aspects: one is affinity and the other is stability. The anti-HIV drug (saquinavir) showed good affinity, but not good stability. Montelukast, on the other hand, was found to bind strongly and stably to Nsp1, allowing the host cells to resume normal protein synthesis,” Tanweer Hussain, Assistant Professor in the Department of Molecular Reproduction said in a statement.
The researchers also tested the effect of the drug on live viruses, in the Bio-Safety Level 3 (BSL-3) facility at the Centre for Infectious Disease Research (CIDR). “Clinicians have tried using the drug and there are reports that said that montelukast reduced hospitalisation in COVID-19 patients,” says Hussain, adding that the exact mechanisms by which it works still need to be fully understood.