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 one 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), that can be repurposed to treat Covid-19.
Using computational biology techniques, 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 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. It is a great interactor with other proteins as well,” 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.
Researchers said narrowing down to these 33 molecules, which have exhibited stability and strong interaction with the Sars-Cov-2 protein, will save significant time on toxicity tests because some are used in FDA-approved drugs such as Remdesivir — currently being repurposed — while small molecules are mostly found in plants.
In the virtual screening of the molecules with NSP1, the team described FDA-approved anti-viral drugs such as Remdesivir and Edoxudine as “promising” as Covid-19 treatment. Esculin and Acarbose, which are prescribed for inflammation and diabetes respectively but are not anti-viral drugs, were also found to have potential to inhibit the protein.
{{/usCountry}}In the virtual screening of the molecules with NSP1, the team described FDA-approved anti-viral drugs such as Remdesivir and Edoxudine as “promising” as Covid-19 treatment. Esculin and Acarbose, which are prescribed for inflammation and diabetes respectively but are not anti-viral drugs, were also found to have potential to inhibit the protein.
{{/usCountry}}The 33 molecules which displayed stability in their interaction with NSP1 are found in lactose, glycyrrhizic acid from liquorice plant (also referred to as athimathuram or yastimadhu); corilagin from pomegranates; galangan from blue ginger (also referred to as galangal or sitharathai); and gingeronone and shogaol from both ginger and blue ginger.
Having started work based on new computational research since early March, the team said identifying 33 molecules will also translate into saving time, money and effort in experimental examinations.
“We have recommended a set of promising small molecules to bind to NSP1. We hope some of these ligands (molecules) could be useful to combat Covid-19,” said Sowdhamini.
Over the last three months, the team used computational docking algorithms to investigate how the ligands (molecules) would interact to 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.
Sharma added, “After two rounds of filters, the top-ranking molecules were considered. These docking runs took approximately 20 days of computing time, followed by analysis and literature survey”.
Vikas Tiwari, PhD student of the laboratory and the one who performed molecular dynamics simulations to yield the small molecules with the most stable interactions with the NSP1 protein, said, “We found that the small molecule or ‘ligand’ stays on with the protein and does not fly away during our simulations.”