Table 2.

Validated and potential drug targets and known NP inhibitors against Coronaviridae. Roman numbering corresponds to numbering in Figure1. Numbers in parenthesis corresponds to structures in Figures 5–10

	Number	Target Protein	Function	Natural Product Inhibitors	NP-Inspired Inhibitors
Viral Proteins	l	Spike Glycoprotein	Host cell recognition	Griffithsin (2), Emodin (3)	EK1 and other Spike fragments
	II	Main Protease (Mpro/3CLpro)	Viral protein mauration	Herbacetin (13), Rhoifolin (15), & other flavonoids	Peptidomimetics
				Tomentin A-E (16), Hirsutenone (17),
	lll	Papain-Like Protease (PLpro)	Viral protein mauration	Tanshinones (19), Psoralidin (18), and	Inhibitors Needed
				Others
	IV	RNA-dependent RNA polymerase (RdRp)	Viral RNA replication	Inhibitors Needed	Favipiravir (22), Remdesivir (1), Ribavirin (23), Galidesivir (24), |3-D-N4-Hydroxycytidine (25)
	V	NSP1	Obstructs host cell protein synthesis and innate immune response	Inhibitors Needed	Inhibitors Needed
	VI	NSP13	Vrial helicase	Myricetin (26), Scutellarein (27)	Inhibitors Needed
	VII	Orf8b	Obstructs innate immune response	Inhibitors Needed	Inhibitors Needed
Host Proteins	VIII	TMPRSS2	Cell membrane protease. Cleaves viral spike protein facilitating membrane fusion & entry	Aprotinin (34)	Inhibitors Needed
	IX	Cathepsin L	Endosomal protease. Cleaves spike protein facilitating membrane fusion	Gallinamide A (35), Nicolaidesin C (36), Grassypeptolide (37), E-64, Leupeptin (38)	Other Reviews