The plant comprises 29 natural secondary metabolites commonly called as ‘withanolides’ extracted from leaves, stems, roots, and flowers which are known for their potent anti-tumor effect (Table 1). Some previous studies have reported the anti-influenza properties of active constituents of WS against H1N1 influenza and antiviral activity of withanone from WS against novel coronavirus (Balakrishnan et al., 2014; Cai et al., 2015; Varshney et al., 2020). However, still, not much is known regarding the antiviral activity of WS phytoconstituents. Therefore, one of the main aims of the present study was to evaluate the antiviral activity of WS phytoconstituents against major target proteins of SARS-CoV-2, the causal agent of the ongoing pandemic.