Montelukast sodium hydrate was suggested by the researchers as a lead chemical for the development of powerful inhibitors to aid in the battle against SARS-CoV-2 infection.
The severe coronavirus disease-19 (COVID-19) pandemic’s etiological agent, SARS-CoV-2, is an enveloped positive-strand RNA virus that is a member of the coronavirus family, which is a wide group of viruses. It is also known as coronavirus 2, the severe acute respiratory illness.
The N-terminal domain and C-terminal helices of the SARS-CoV-2 non-structural protein 1 (Nsp1) are joined by a brief linker region. The 40S ribosomal subunit’s messenger ribonucleic acid (mRNA) entry channel binds to the C-terminal helices of Nsp1 (Nsp1-C-ter) from SARS-CoV-2, blocking mRNA entrance and stopping host protein synthesis.
Nsp1 is essential for viral replication and inhibits the host immune system.
Nsp1 therefore seems to be a desirable therapeutic target. In the study, 12 medications that had been given the green light by the U.S., FDA were evaluated in silico against Nsp1’s C-terminal helices ( Nsp1-C-ter ). Montelukast sodium hydrate was one of the 12 medications retrieved, and following a series of tests.
It was reported and discovered to:
- In vitro, bind to Nsp1 with a high binding affinity.
- Binds energy in simulation runs to form a stable compound with Nsp1-C-ter.
- Restores Nsp1’s inhibition of host protein synthesis, as shown by the expression of the firefly luciferase reporter gene in living organisms.
- Importantly, in HEK cells expressing ACE2 and Vero-E6 cells, exhibits antiviral effectiveness against SARS-CoV-2 with minimal viral multiplication.