Targeting Nsp9 as an anti-SARS-CoV-2 strategy (Electronic supplementary information (ESI) available. See DOI: 10.1039/d0nj04909c)

ABSTRACT

Non-structural protein 9 (Nsp9) plays a key role in viral replication of coronavirus and represents a promising target for anti-SARS-CoV-2 strategies. In order to find pockets with potential druggability, four binding-site search methods were employed. One potentially druggable pocket was found and compared to a pocket database to search for similar pockets of viral proteins containing co-crystallized small-molecules. This resulted in 16 molecules with known antiviral activity that were subsequently analyzed by molecular docking using both the dimer and monomer forms of Nsp9 as receptors. Using these molecules as probes, the binding site was mapped according to the amino acids and to their specific interactions involved in harboring these compounds. Molecular dynamics simulations suggested that the dimer and monomer forms are stable and pointed to a reduced flexibility of the monomer compared to the dimer. The pocket of the monomer was also shown to be more accessible and more prone to small-molecule binding.