Researchers identify 33 molecules that can target 1 Covid protein

MUMBAI: Researchers at the Bengaluru-based National Centre for Biological Sciences (NCBS) have identified 33 small molecules out of 3, 30,000 that can target the protein NSP1 in the Sars-cov-2 virus, which causes Covid-19. Identifying these molecules may help with drug discovery and examining existing drugs, approved by the Food and Drug Administration (FDA), so that they can be repurposed to treat Covid-19. The three-member team at NCBS, which is a biological centre of the Tata Institute of Fundamental Research, found that only one in 10,000 screened molecules has the potential to target the protein. The team started its work based on new computational biology techniques in early March.

“The choice of target protein, NSP1, is both unique among research at this time and important based on the role the NSP1 protein plays. It stalls host gene expression, could degrade host MRNA, and protects viral (self) MRNA from degradation,” said R Sowdhamini, professor of biochemistry, NCBS, and corresponding author of the study which has been accepted by the Journal of Biosciences of the Indian Academy of Sciences.

The 33 molecules are found in elements found in natural ingredients like the liquorice plant, pomegranate, blue ginger and ginger. In the virtual screening of the molecules that exhibited stability and strong interaction with NSP1, the team described Fdaapproved anti-viral drugs such as Remdesivir and Edoxudine to be “promising” as Covid-19 treatment. Esculin and Acarbose, conventionally prescribed for inflammation and diabetes, also exhibited potential to inhibit the NSP1.

Researchers said narrowing down to these 33 molecules will save time on toxicity tests. Over the last three months, the team used computational docking algorithms to investigate how these molecules, known as ligands, would inhibit the protein.“scores were provided depending on the strength of favourable and unfavourable interactions. More negative the scores, higher the chance for that molecule to be a potential inhibitor for the NSP1 protein,” said Abhishek Sharma, a joint PHD student in two laboratories and first author of the study.

Vikas Tiwari, PHD student of the laboratory and one who performed molecular dynamics simulations to yield small molecules with the most stable interactions with the NSP1, said, “We found the small molecule or ‘ligand’ stays on with the protein and does not fly away during our simulations.”