Development of nucleotide analogs library by performing virtual screening using molecular docking methodologies at the active site of RNA dependent RNA polymerase enzyme of SAS-COV-2
The active site of RNA dependent RNA polymerase enzyme needs to be defined using (PDB: 6M71,7BV2) to identify new RdRp inhibitors. Reports suggest that Remdesivir is a potential good inhibitor, hence virtual screening of chemical databases could be way forward to identify analogs of Remdesivir and its metabolites. Any derivatives of the nucleic acid bases which have sugar (or analog) linkages and hydrolysable phosphate/phosphonamide/phosphoramidite based molecules could be potential hits. Pharmacophore perception methods might be helpful and participants may consider six features, i.e., hydrogen bond donor, hydrogen bond acceptor, hydrophobic, ring aromatic, positive ionizable and negative ionisable for pharmacophore perception. De novo design, Lipinski type empirical rules, or many virtual screens should be used to design a library of new molecules. Later, Molecular docking-based virtual screening of a library of nucleotide analogs needs to be carried out (towards the end of the VS exercise) by using active site of RNA dependent RNA polymerase enzyme (PDB: 6M71, 7BV2) to identify new RdRp inhibitors with best docking scores and binding energies for the top 100 molecules.