Pharmacophore based virtual screening, molecular docking, molecular dynamics and MM-GBSA approach for identification of prospective SARS-CoV-2 inhibitor from natural product databases

• DOI: 10.1080/07391102.2020.1824814
• Publication Date: 2020-09-28T07:42:58Z
• Authors: Banoth Karan Kumar; Faheem; Kondapalli Venkat...; Rupal Ojha; Vijay Kumar Praja...; Aravinda Pai; Sankaranarayanan ...
• Keywords: Docking (animal); Natural product; DOCK; Molecular mechanics

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily appeared in Wuhan, China, December 2019. At present, no proper therapy and vaccinations are available for the disease, it is increasing day with a high mortality rate. Pharmacophore based virtual screening of selected natural product databases followed Glide molecular docking dynamics studies against SARS-CoV-2 main protease was investigated to identify potential ligands that may act as inhibitors. The molecules SN00293542 SN00382835 revealed highest score -14.57 -12.42 kcal/mol, respectively, when compared co-crystal PDB-6Y2F (O6K) 6W63 (X77) Mpro. To further validate interactions top scored SN00382835, study 100 ns carried out. This indicated protein-ligand complex stable throughout simulation period, minimal backbone fluctuations have ensued system. Post-MM-GBSA analysis data showed free binding energy-71.7004 +/- 7.98, -56.81+/- 7.54 respectively. computational identified several inhibitors top-ranked SN00293542, occupied active site target, like ligand. These emerge promising thus needs detailed investigations. Communicated Ramaswamy H. Sarma.