Identification of the binding interactions of some novel antiviral compounds against Nsp1 protein from SARS-CoV-2 (COVID-19) through high throughput screening

• Published in: Journal of biomolecular structure & dynamics Vol. 40; no. 14; pp. 6634 - 6641
• Main Authors: Chowdhury, Nilkanta, Bagchi, Angshuman
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 22.09.2022
• Subjects: docking; drug designing; molecular dynamics simulations; Nsp1; SARS-CoV-2; virtual screening; virulence factors; molecular dynamics simulations; docking; SARS-CoV-2; Nsp1; virtual screening; drug designing; virulence factors
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.1887763

The SARS-CoV-2 pandemic has become a global threat. It has become very difficult to control the spreading of the virus. The virus is a RNA virus and the virulence of the virus is mediated by three virulence causing proteins, viz., Nsp1, Nsp3c and ORF7. So far the drug designing endeavors against the virus have been being targeted towards the spike protein which is responsible for the entry of the virus inside human host as well as the RNA dependent RNA polymerase. However, no effective treatment against the virus has so far been developed. In the present situation, an attempt has been made to target the virulence protein factor Nsp1 which binds to the 40S ribosomal subunit of the human host. We tried to target the Nsp1 by in-silico virtual screening of ligand libraries. We built the three dimensional structure of Nsp1 and used the structure to screen the ChEMBL drug library. We used molecular docking simulations of the top6 screened ligands with Nsp1 and subjected the liagnd-Nsp1 complexes to molecular dynamics simulations to analyze the behaviors of the ligands in a virtual cell. From our analysis we could predict that the ligands bearing the ChEMBL identifiers, CHEMBL1096281, CHEMBL2022920, CHEMBL175656, had the best binding affinity values with Nsp1. Therefore, these ligand molecules may be tested in wet-lab for further analysis. This is the first report to target the virulence factor Nsp1 from SARS-CoV-2. Communicated by Ramaswamy H. Sarma