Table 2.

Withania somnifera and its phytochemicals and associated molecular mechanisms of their therapeutic effects against SARS-CoV-2.

Phytochemical	Source	Molecular Mechanism	Reference
Withaferin A	Not Available	Inhibited SARS-CoV-2 Mpro, thus preventing SARS-CoV-2 replication	[90]
	Not Available	Inhibited SARS-CoV-2 Mpro and structural proteins, including S, E, and N, thus impeding viral replication and entry into host cells	[93]
	Purchased from Sigma-Aldrich (now Merck, St. Louis, MO, USA)	Inhibited SARS-CoV-2 Mpro, thus disrupting SARS-CoV-2 replication	[94]
	Not Available	Inhibited TMPRSS2 receptor, thereby preventing viral entry into host cells	[95]
	Not Available	Inhibited SARS-CoV-2 Mpro and GRP78, thus impeding viral replication and SARS-CoV-2 recognition by host cells	[96]
Withanolide A	Leaves, stems, roots, and flowers extract	Inhibited SARS-CoV and SARS-CoV-2 S protein, SARS-CoV 3CL-pro main protease, and SARS-CoV-2 NSP10/NSP-16 complex, thus decreasing viral recognition and replication in host cells	[97]
Withanolide B	Not Available	Inhibited SARS-CoV-2 Mpro and structural proteins, including S, E, and N.	[93]
Withanolide R	Not Available	Inhibited main protease (NSP5) of SARS-CoV-2, consequently reducing the survival of SARS-CoV-2	[98]
2,3-Dihydrowithaferin A	Not Available	Inhibited SARS-CoV-2 S protein and acted as the most potent S protein inhibitor as compared with the other WS phytochemicals, preventing viral entry into host cells	[98]
Withanone	Not Available	Inhibited TMPRSS2 receptor and downregulated TMPRSS2 mRNA, thereby impeding SARS-CoV-2 entry into host cells	[95]
	Not Available	Inhibited SARS-CoV-2 main protease 3CL-pro and S protein, thus decreasing viral entry and replication in host cells	[99]
	Leaves and stem extract	Inhibited SARS-CoV-2 TMPRSS2 and Mpro, thus prohibiting SARS-CoV-2 entry and replication in host cells	[100]
	Not Available	Inhibited SARS-CoV-2 Mpro, thus halting SARS-CoV-2 replication in host cells	[101]
	Root extract	Inhibited viral entry by attenuating the interaction between the host ACE2 receptor and RBD located in the SARS-CoV-2 S-protein	[102]
	Purchased from Sigma-Aldrich (now Merck, St. Louis, MO, USA) (>98% purity)	Inhibited SARS-CoV-2 Mpro, thus disrupting SARS-CoV-2 replication	[94]
Withanoside IV	Root extract	Abrogated NSP10-NSP16 switching mechanisms in SARS-CoV-2, thus promoting fatality of SARS-CoV-2	[103]
Withanoside V	Not Available	Inhibited SARS-CoV-2 Mpro, thus attenuating SARS-CoV-2 replication in host cell	[104]
	Not Available	Inhibited SARS-CoV-2 Mpro, thus attenuating SARS-CoV-2 replication in host cells	[105]
Withanoside X	Not Available	Inhibited SARS-CoV-2 NSP15 endoribonuclease and SARS-CoV-2 S protein, thus preventing SARS-CoV-2 entry and replications in host cells	[106]
Quercetin glucoside	Not Available	Inhibited SARS-CoV-2 NSP15 endoribonuclease and SARS-CoV-2 S proteins, thus reducing SARS-CoV-2 entry and replication in host cells	[106]
Somniferin	Not Available	Inhibited SARS-CoV-2 Mpro, thus attenuating SARS-CoV-2 replication in host cells	[104]