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Table 2 Anti-EV71 effects of pure compounds from Chinese medicines

From: Chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity

Category Compound and reference Chemical structure Plant source Chemical class Anti-EV71 effect Mechanism
Flavones Apigenin [65] Ocimum basilicum (Luo Le), etc Flavone Reduces CPE (EC50 25.5 μM, SI 8.7), viral protein expression, ROS generation, cytokine up-regulation Interferes with viral IRES activity, JNK activation, association of EV71 RNA with hnRNP A1 and A2 proteins
Chrysosplenetin [67] Laggera pterodonta (Chou Ling Dan) Flavonol Reduces CPE (EC50, 0.17 μM, SI 107.5), plaque formation, production of viral VP1 protein, and the viral yield Shows strong antiviral potency targeting the post-attachment stage
Penduletin [67] Laggera pterodonta (Chou Ling Dan) Flavonol Reduces CPE (EC50 0.17 μM, SI 655.5), plaque formation, production of viral VP1 protein, and the viral yield Shows strong antiviral potency targeting the post-attachment stage
7,8-dihydroxyflavone [76] Chrysanthemum morifolium Ramat (Ju Hua), etc Flavone Shows 20 % cytotoxicity, 80 % CPE reduction and 40 % IRES activity at 50 μM  
Kaempferol [76] Chrysanthemum morifolium Ramat (Ju Hua), etc Flavonol Shows 20 % cytotoxicity, 80 % CPE reduction and 40 % IRES activity at 50 μM, reduces virus yield, and viral protein expression Changes the expression level of FUBP1, FUBP3, HNRPD, HNRH1 and HNRPF proteins, which may contribute to the anti-EV71 activity
Quercetin [76] Chrysanthemum morifolium Ramat (Ju Hua), etc Flavonol Shows 20 % cytotoxicity, 80 % CPE reduction and 40 % IRES activity at 50 μM  
Hesperetin [76] Chrysanthemum morifolium Ramat (Ju Hua), etc Flavonone Shows 20 % cytotoxicity, 80 % CPE reduction and 40 % IRES activity at 50 μM  
Hesperidin [76] Chrysanthemum morifolium Ramat (Ju Hua), etc Flavonone glucoside Shows 20 % cytotoxicity, 80 % CPE reduction at 50 μM  
Eupafolin [37] Kalanchoe gracilis (Deng Long Cao) Flavone Reduces CPE (EC50 0.44 μM, SI 808), plaque formation, decreases virus-induced IL-6 and RANTES expression, and decreases the phosphorylation of cytokine induction-related proteins Inactivates the virus, and suppresses proinflammatory cytokines
Chrysin [79] Oroxylum indicum (L.)Vent. (Mu Hu Die), Pinus mon-ticola Dougl. (Bai Shan Song) Flavone Reduces CPE (EC50 10 μM, SI 20), viral RNA, capsid protein, and infectious virions Inhibits viral 3C protease
Chrysin phosphate ester [79] Synthesised Flavone derivative Reduces CPE (EC50 6 μM, SI 33), viral RNA, capsid protein, and infectious virion Inhibits viral 3C protease
Luteolin [64, 80] Lonicera japonica (Jin Yin Hua), Dendranthema indicum (Ye Ju Hua) Flavone Reduces CPE (EC50 31.56 μM, SI 9.25 in RD cells), inhibits viral RNA replication Targets post-attachment stage
Rutin [38] Saururus chinensis (Lour.) Baill (San Bai Cao) Flavonoid glycoside Reduces CPE (200 μM), viral RNA level, and virus titre Inhibits activation of MEK1-ERK signalling pathway
Formononetin [82] Trifolium pratense (San Ye Cao), etc Isoflavone Reduces CPE (EC50 3.98 μM, SI 43.07), viral RNA replication, protein synthesis Suppresses ERK, p38, and JNK activation, and COX-2/PGE2 expression
Terpenes Ursolic acid [63] Ocimum basilicum (Luo Le) Triterpenoid Reduces CPE (EC50 1.1 μM, SI 200) Inhibits viral infection and replication process
Linalool [65] Ocimum basilicum (Luo Le) Monoterpene Reduces CPE (EC50 273.60 μM, SI 4.2)  
Raoulic acid [84] Raoulia australis Diterpene Reduces CPE (EC50 0.25 μM, SI above 658)  
Glycyrrhizic acid [87] Glycyrrhiza uralensis (Gan Cao) Triterpenoid Reduces plaque formation at 3, 5 μM and virus titre and expression of viral VP1 protein Targets post-viral entry process
Geniposide [88] Fructus gardeniae (Zhi Zi) Monoterpene Reduces CPE, viral RNA level, plaque formation, and inhibited viral IRES activity  
GLTA [91] Ganoderma lucidum (Ling Zhi) Triterpenoid Reduces CPE (EC50 below 0.16 μg/mL) Blocks adsorption and uncoating
GLTB [91] Ganoderma lucidum (Ling Zhi) Triterpenoid Reduces CPE (EC50 below 0.16 μg/mL) Blocks adsorption and uncoating
Hederasaponin B [92] Hedera helix (Chang Chun Teng) Triterpenoid Reduces CPE (EC50 24.77 μM, SI 2.02) and viral capsid protein expression Inhibits viral capsid protein expression
Ginsenoside Rg2 [95] Panax ginseng Meyer (Ren Shen) Triterpenoid Reduces CPE  
Polyphenols Epigallocatechin gallate (EGCG) [96] Camellia sinensis (Lv Cha) Polyphenol Reduces plaque formation, viral RNA level, and raises the survival rate of Vero cells approximately fourfold relative to untreated infected cells at 25 μM Has antioxidant activity, and suppresses viral RNA replication
Gallocatechin gallate (GCG) [96] Camellia sinensis (Lv Cha) Polyphenol Reduces plaque formation, and raises the survival rate approximately fourfold higher than the infected group at 25 μM  
Geraniin [99] Geranium thunbergii (Lao Guan Cao) Tannin Reduces CPE, viral yield, can improve survival and clinical score in infected mice (EC50 10.5 μM, SI 20)  
Chebulagic acid [102] Terminalia chebula (He Zi) Tannin Reduces CPE, and reduces the mortality of infected mice, relieves the symptoms (EC50 13.1 μM, SI 16) Inhibits viral replication
Corilagin [41] Phyllanthus urinaria (Zhen Zhu Cao) Ellagitannins Reduces CPE (EC50 5.6 μg/mL)  
Punicalagin [103] Punica granatum L. (Shi Liu) Tannin Reduces CPE (EC50 15 μg/mL), viral RNA level, and mice mortality in vivo  
Steroids Timosaponin B-II [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 4.3 μM, SI 92.9)  
Anemarrhenasaponin II [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 22.2 μM, SI 3.8)  
Timosaponin G [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 9.1 μM, SI 2.3)  
Timosaponin A-IV [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 4.7 μM, SI 2.2)  
Timosaponin A-III [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 1.1 μM, SI 2.4)  
Shatavarin IV [105] Anemarrhena asphodeloides (Zhi Mu) Steroidal saponin Reduces CPE (EC50 2.2 μM, SI 1.8)  
Miscellaneous Gallic acid [113] Woodfordia fruticosa (Xia Zi Hua) Phenolic acid Reduces CPE (EC50 4.47 μM, SI 99.57) Has antioxidant activity
Resveratrol [116, 117] Vitis vinifera L. (Pu Tao), Polygonum cuspidatum Sieb.et Zucc.(Hu Zhang), Fructus mori (Sang Shen), Arachis hypogaea Linn. (Hua Sheng), Veratrum grandiflorum (Mao Ye Li Lu) Phenol Reduces CPE (EC50 20.2 mM, SI 15.2) Blocks IKKs/NF-κB signalling pathway
Allophycocyanin [120]   Spirulina platensis Protein Reduces CPE (EC50 0.045 μM, SI 36.7), plaque formation (EC50 0.056 μM, SI 29.5), delays viral RNA synthesis, and inhibits EV71-induced apoptosis Interferes with early stage of viral replication
Caffeic acid [36] Kalanchoe gracilis (Deng Long Cao) Phenol Reduces CPE (EC50 23.87 μM, SI 11.51), plaque formation  
Aloe-emodin [124] Rheum palmatum (Da Huang) Anthraquinone Induces IFN expression, activates NO production, and reduces plaque formation (EC50 0.5-1.9 μM, SI above 5540) Activates type I and II IFN signalling pathways against viral replication
Garlicin [127] Allium Sativum (Da Suan) Diallyl disulfide Reduces CPE (EC50 99.95 μM, SI 44.66)  
Oblongifolin J [128] Garcinia oblongifolia (Ling Nan Shan Zhu Zi) Prenylated benzoylphloroglucinol Reduces CPE (EC50 31.1 μM, SI 1.5)  
Oblongifolin M [128] Garcinia oblongifolia (Ling Nan Shan Zhu Zi) Prenylated benzoylphloroglucinol Reduces CPE (EC50 16.1 μM, SI 2.4)  
Euxanthone [128] Garcinia oblongifolia (Ling Nan Shan Zhu Zi) Xanthone Reduces CPE (EC50 12.2 μM, SI 3.0)  
Gramine derivative 4 s [130] Synthesised Indole alkaloid Reduces CPE (EC50 9.1 μM, SI 14.3), viral RNA replication, protein synthesis, and virus-induced apoptosis Inhibits viral adsorption or affects viral release from the cells
Chlorogenic acid [131] Lonicera japonica (Jin Yin Hua), Eucommia ulmoides Oliv. (Du Zhong), Lythrum salicaria L. (Qian Qu Cai) Aromatic acids Reduces plaque formation (EC50 6.3 μg/mL) Inhibits EV71 2A transcription and translation
Magnesium lithospermate B [132] Salvia miltiorrhiza (Dan Shen) Aromatic acids Reduces CPE (EC50 0.09 mM, SI 10.52), plaque formation, protein expression Influences virus infection, and IRES activity
Rosmarinic acid [132] Salvia miltiorrhiza (Dan Shen) Aromatic acids Reduces CPE (EC50 0.50 mM, SI 2.97), plaque formation, protein expression Influences virus infection, and IRES activity
Matrine [137] Sophora flavescens (Ku Shen) Gordon landmines ketoneses alkaloid Reduces viral RNA level, and mice mortality in vivo  
Lycorine [145] Lycoris radiata (Shi Suan) Benzylphenethylamine alkaloid Reduces CPE (EC50 0.48 μg/mL, SI above 100), viral RNA level, and mice mortality in vivo Influences viral protein expression