Systematic structure guided clustering of chemical lead compounds targeting RdRp of SARS-CoV-2

• DOI: 10.23736/s2724-542x.22.02869-3
• Publication Date: 2022-09-16T12:20:04Z
• Authors: Ahmad ALSULIMANI; Tulika BHARDWAJ; Essam M. JANAHI; Atiah H. ALMALKI; Brij N. TEWARI; Mohd WAHID; Mustfa F. ALKHANANI; Pallavi SOMVANSHI; Shafiul HAQUE
• Keywords: Docking (animal); Drug repositioning; DOCK; Drug target

BACKGROUND: To combat the global health issue caused by SARS-CoV2, scientists are attempting various therapeutic approaches towards drug discovery including computational biology and drug-repurposing. Recent studies have highlighted conserved nature of RNA-dependent RNA polymerase (RdRp) coronaviruses affecting human, bat animals. In this study attempts been made to identify potential inhibitors RdRp utilizing molecular docking MD simulation studies.METHODS: Systematic structure-based screening chemical compounds from public libraries was performed lead molecules inhibiting RdRp. This structure driven clustering is based on decision tree model generated combining two properties: 1) shape descriptors; 2) critical number multiple bonds. The enabled subjected followed dynamics studies.RESULTS: results revealed that stability protein-drug complex in order RdRp-Oxoglaucine >RdRp-Flutroline >RdRp-Brucine complex.CONCLUSIONS: identifies Oxoglaucine, Brucine Flutroline as prospective agents SARS-CoV-2 further warrants for experimental validation.