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 |