Methods

ACE2 interaction network and hypothesis
ACE2 is the proposed attachment site for SARS-CoV-2 in humans. Protein interaction studies were conducted around this protein to understand how the attachment of virus with ACE2 affects the pathology in human system. Computational protein-interaction analysis provides the knowledge about the indirect and probable interactions which might be occurring with the query protein. This is a very useful approach for predicting the new interactions of proteins in the in-vivo system. Cytoscape v3.7.2 (Shannon et al., 2003) was used to design the interaction network. BiNGO plugin was used for the analysis and prediction of overrepresented pathways in master network (Maere et al., 2005). Overrepresented pathways are the set of pathways which are collectively taken-up by the set of proteins under study. This helps in understanding the final fate of protein-interactions.

Pharmaco-networking of N. sativa constituents
Literature mining was done to find the different constituents of N. sativa. Their PubChem IDs (Kim, et al.) were retrieved, and constituents (ligands) were downloaded in .SDF format. QikProp v6.3 (rel 13) was used to perform computational ADME analysis (Schrödinger Release 2020-1: QikProp, Schrödinger, LLC, New York, NY, 2020). ADME stands for Absorption, Distribution, Metabolism and Excretion. It was performed to predict the druggability of the compounds. Further, receptors were predicted for constituents of N. sativa in human system by using Swiss target prediction tool (Gfeller et al., 2014). These receptors were additionally used to analyse their mode of action via interaction analysis.

Docking studies
ACE2 was downloaded from PDB database in Maestro v12.3 environment (Schrödinger Release 2020-1: Maestro, Schrödinger, LLC, New York, NY, 2020) and prepared for docking analysis. All the ligands of N. sativa were processed by using LigPrep (Schrödinger Release 2020-1: LigPrep, Schrödinger, LLC, New York, NY, 2020) to generate all the possible stereoisomers. Extra-Precision (XP) docking was performed using Glide (Schrödinger Release 2020-1: Glide, Schrödinger, LLC, New York, NY, 2020). Docking analysis was performed to analyse the best binding ligand from N. sativa constituents to ACE2 receptor.