Docking studies of the selected WS phytoconstituents were carried out with human ACE2 receptor, SARS-CoV and SARS-CoV-2 specific proteins. The catalytically active sites of SARS-CoV-2 specific proteins were targeted in order to obtain the binding energy involved in the complex formation and to discover the molecular mechanisms responsible for specific inhibition of targets. Tables 5–11 summarize the predicted binding energies and dissociation constants (Kd) of WS phytoconstituents with respect to specific human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases viz. 3CL-pro and PL-pro. The binding sites of the WS phytoconstituents on the selected viral target proteins as well as the interacting amino acids were predicted to be almost the same by the three molecular docking softwares (Tables 5–11). The common interacting amino acids between the three softwares have been written in italicized form in Tables 5–11. As is evident from Tables 5–11, most of the WS phytoconstituents exhibited potent binding kinetics to the above-mentioned proteins. Docking analyses using AutoDock 4.0/ADT version 4.2.6 program revealed that the binding affinities of the WS phytoconstituents for the human ACE2 receptor decreased in the order withanolide B > withanolide A > withanolide E > viscosalactone B > withaferin A > anaferine > withanolide D > withanone > withasomnine. Withanolide B exhibited a 1000× stronger binding to human ACE2 receptor (Table 5; BE: −10.21 kcal/mol, Kd: 32.78 nM) as compared to standard reference drugs, arbidol (Table 5; BE: −6.69 kcal/mol, Kd: 12.47 µM) and losartan (Table 5; BE: –6.72 kcal/mol, Kd: 11.86 µM). Withanolide B also exhibited potent binding to papain like protease of SARS-CoV-2 (Table 8; BE −10.3 kcal/mol, Kd: 28.32 nM) as compared to procainamide (Table 8; BE −5.03 kcal/mol, Kd: 206.96 µM) and cinacalcet (Table 8; BE −6.44 kcal/mol, Kd: 19.17 µM).