Fig. 2.

A flowchart of the integrated evolution and structure guided workflow as discussed in this manuscript. The proposed workflow has two components: first, the identification of a critical region of RBD based on a combination of evolutionary and structural studies (pink); and second, a druggability assessment of small molecule leads targeting the above critical region (blue). In the first section (pink), we performed the mentioned analyses to identify the region of RBD that is evolutionarily very much significant. Also, we performed Structural analysis to find out important Structure Block (SB) from structural perspective. Then we combined these two information by applying Fuzzy Clustering analysis and identified the most important SB in the RBD which can be used as the druggable pocket. Then in the second section (Blue region), we validated the residues of the identified important SB as potential drug binding sites, considered drug molecules from database, selected top 100 molecules and performed Docking study and Metadynamic Simulation to select potential drug candidate against Covid-19. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)