Table 1.

Summary of the pathogenesis of COVID-19 and therapeutic mechanisms of CHM.

Disease	Pathogenesis	Chinese herbal formulas and active components	Targets and signaling pathways	References
Severe viral infection	Virus replication	Lianhua Qingwen formula; Wogonin (Scutellariae Radix); Baicalin (Scutellariae Radix); L-methylephedrin, L-ephedrine, and D-pseudo-ephedrine (Ephedrae Herba); and patchouli alcohol (Pogostemonis Herba)	Inhibiting SARS-CoV-2, SARS-CoV, influenza A and B virus replication, inducing IFN-γ, modulating Toll-like receptors (TLRs), retinoic acid inducible gene-1 (RIG-1), adenosine monophosphate (AMP)-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathways	[23], [24], [25], [26], [27]
	Viral RNA synthesis	HouttuyniaeHerba	Inhibiting SRAS-CoV RdRp	[28]
	Virus invasion	Qingfei Paidu decoction and Huoxiang Zhengqi oral liquid, patchouli alcohol, tussilagone (Farfarae Flos), ergosterol, asarinin (Asari Radix et Rhizoma), ephedrine hydrochloride (Ephedrae Herba), shionone (Asteris Radix et Rhizoma), quercetin, isorhamnetin (Glycyrrhizae Radix et Rhizoma), and irisolidone (PogostemonisHerba)	Binding to ACE2 receptor	[29], [30]
	Viral protein proteins and particle assembly	Houttuyniae Herba, Qingfei Paidu decoction and Huoxiang Zhengqi oral liquid, patchouli alcohol (Pogostemonis Herba), saikosaponin B (Bupleuri Radix), ergosterol (Polyporus), shionone (Asteris Radix et Rhizoma), 23-acetate alisol B (Alismatis Rhizoma), licorice glycoside E, kaempferol, (2R)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-ketone, quercetin, isorhamnetin (Glycyrrhizae Radix et Rhizoma), naringenin (Citri Reticulatae Pericarpium), robinin (Platycodi Radix) and irisolidone (PogostemonisHerba), herbacetin (Rhodiolae Crenulatae Radix et Rhizoma), rhoifolin, apigenin, luteolin (Citri Reticulatae Pericarpium), quercetin, daidzein, and puerarin (Puerariae Radix)	Binding to 3CLpro and inhibiting the proteolytic activity of SARS-CoV 3CLpro	[28], [29], [30], [31]
Inflammation and cytokine storm	Virus-infected alveolar cells release signals to recruit and activate immune cells, which secrete a variety of cytokines and chemokines and destroy the virus by releasing inflammatory mediators or phagocytosis. The excessive immune response initiates a “cytokine storm” that causes damage of lung tissue and exacerbation of pneumonia	Lianhua Qingwen capsule, Lonicerae Japonicae Flos, platycodin D (Platycodi Radix), and Moutan Cortex Radicis	Suppressing pro-inflammatory cytokines production	[32], [33], [34], [35]
		Lonicerae Japonicae Flos	Enhancing anti-inflammatory cytokines production	[33]
		Platycodin D (Platycodi Radix)	Suppressing apoptosis	[34]
		Platycodin D (Platycodi Radix) and Moutan Cortex Radicis	Strengthening antioxidant	[34], [35]
		Platycodin D (Platycodi Radix) and Moutan Cortex Radicis	Protecting host against acute lung injury	[34], [35]
		Polysaccharides of Pinelliae Rhizoma	Regulating IL-4 and IFN-γ	[36]
Prevention of pulmonary fluids and obstruction	Acute lung inflammation increases the permeability of lung endothelial and epithelial barriers, impairs alveolar fluids clearance mechanisms, causes edema, blocks airways, and leads to hypoxia	Asteris Radix, Fritillaria cirrhosae Bulbus, Trichosanthis Fructus, Eriobotryae Japonicae Folium, polysaccharides of Pinelliae Rhizoma, and verticine	Dispelling phlegm and relieving cough, inhibiting mucus secretion in human airway epithelial cells	[36], [37], [38], [39]
Multi-organ dysfunction	ACE2 receptor attack, immune destruction	Astragalus and Angelica, Rheum and its components, and triptolide	Boosting the immune system, relieving diuresis, anti-oxidation, and inflammation	[40]
	Qi deficiency	CodonopsisRadix and Panax ginseng	Replenishing qi–yin deficiency, promoting organ and tissue regeneration and recovery	[21], [40], [41]
	Activation of the airway inflammatory pathway	Xiyanping injection (andrographolide sulfonate)	Ameliorating airway inflammatory cell recruitment and inhibiting nuclear factor (NF)-κB and MAPK-mediated inflammatory responses	[42]
	Over-secretion of inflammatory cytokines	Xuebijing injection (Carthamus tinctorius, Ligusticum wallichii, and Salvia miltiorrhiza)	Suppressing inflammatory cytokine secretion	[43]
Lung fibrosis	Induction of lipogenesis	Naringenin	Inhibiting autophagy and suppressing lung inflammation and fibrosis	[44]
	Wnt signaling activation	Morusin	Alleviating mycoplasma pneumonia via the inhibition of Wnt/β-catenin and NF-κB signaling	[45]
	TGF-β and integrin activation	Yupingfeng formula (Astragalus and Atractylodes macrocephala)	Blocking fibroblast activation, collagen production, and extracellular matrix (ECM) degradation signaling pathway	[46]
	Tissue damage due to viral binding to ACE2	Tanshinone IIA	Attenuating bleomycin-induced pulmonary fibrosis via modulating ACE2	[47]
	p38 MAPK activation	Oxymatrine	Inhibiting phosphorylated p38 MAPK and blocking fibroblast activation and collagen production	[48]
	Activation of ECM	Honokiol	Inhibiting ECM and pro-inflammatory factors	[49], [50]
	Induction of ROS and protein oxidation	Resveratrol and berberine	Acting as ROS scavenger, maintaining redox balance, and preventing of protein oxidation	[51], [52], [53]