TABLE 4.

List of the potent extracts and bioactive compounds that inhibit Rotavirus

Plant name/Active compounds	Virus strain assessed	Test dose	Culture/Animal model assessed	Proposed mechanism	References
Pinus koraiensis Zucc. (seed Shell)	Human rotavirus	250 μg/ml	African rhesus monkey kidney (MA‐104) epithelial cells	Seed shell interferes with virus adsorption by inhibiting CPE of rotavirus in cell cultures	Mukoyama et al., 1991a
Epigallocatechin gallate and theaflavin digallate (green tea)	Human rotavirus (Wa)	IC50 125 μg/ml to 250 μg/ml	MA‐104 cells	Interfered with virus adsorption	Mukoyama et al., 1991b
Lomatium dissectum Nutt.	Bovine rotavirus)	Dilutions ranging from 1 × 10‐l through 1 × l0−7 of 0.2 ml of extract	MA‐104 cells	Inhibited virus induced CPE	McCutcheon et al., 1995
Theobroma cacao Linn. (husk pigment)	Simian rotavirus (SA‐11) strain, human rotavirus strains	1 mg/ml	MA‐104 cells	Interfered with rotavirus adsorption to cells, also inhibited rotavirus intracellular replications and lessened the infectious viral titer	Gu et al., 2000
Hesperidin and neohesperidin (Citrus aurantium Linn.)	Human rotavirus (Wa)	IC50 0.05 mg/ml, 10 μM/ml and 25 μM/ml	MA‐104 cells	Hesperidin and neohesperidin exhibited inhibitory effect on rotavirus infection	Kim et al., 2000
Stevian (Stevia rebaudiana)	Human rotavirus strains and SA‐11	EC50 431–492 μg/ml	MA‐104 cells	Inhibitory activity against the replication of four serotypes of human rotavirus (HRV) and inhibited the binding of VP7 to the infected cells	Takahashi et al., 2001
Stevia rebaudiana Bertoni.	Human rotavirus and SA‐11	EC50 32–153 μg/ml	MA‐104 cells	Inhibitory activity against the virus replication and binding of viral proteins VP7 not VP4 to the infected cells	Takahashi et al., 2001
Artocarpus integrifolia Linn. Myristica fragrans Houtt. and Spongias lutea Linn.	SA‐11 and Human (HCR3) rotaviruses in MA‐104 cells	(480 μg/ml), (160 μg/ml) and (40 μg/ml)	MA‐104 cells	Antiviral activity against both the viruses	Goncalves et al., 2005
280 natural compounds	Rotaviruses	IC50 7.5 μg/ml	MA‐104 cells	18‐β‐glycyrrhetinic acid, abietic acid, alltrans‐retinoic acid, and mangostin reduced the virus replication as well induced the cell signaling pathways involved in antiviral and inflammatory gene expressions	Shaneyfelt et al., 2006
Vaccinium macrocarpon Aiton, (Juice)	SA‐11	1.3, 2.5, 5, 10, 12, 20, 33, and 50% in PBS	MA‐104 cells	Inhibited the rotavirus induced hemagglutination reaction and mediated the anti‐rotavirus activity	Lipson et al., 2007
Aegle marmelos Linn.	SA‐11	0.51 mg/ml ± 0.005 mg/ml, 2.55 mg/ml ± 0.025 mg/ml and 5.11 mg/ ml ± 0.05 mg/ml	MA‐104 cells	Significantly decreased therotoviral infectivity or virus inhibition	Brijesh et al., 2009
Quillaja saponaria Molina.	Rhesus rotavirus	1–1,000 μg/ml	MA‐104 cells	Blocked rotavirus attachment and attenuate infection	Roner et al., 2007
Pectic polysaccharides (Panax ginseng C.A. Mey)	IC50 (15 and 10) μg/m	Human rotavirus (Wa)	MA‐104 cells	Protecting cell viability from rotavirus‐induced infection. It possibly allievated virus proliferation in cells	Baek et al., 2010
Polyphenols (Glycyrrhiza uralensis Fisch)	EC50 of polyphenols were 18.7–69.5 μM against G5P[7] and 14.7–88.1 μM against G8P[7]	Bovine rotavirus G8P[7] and porcine rotavirus G5P[7]	Fetal rhesus Monkey kidney (TF‐104) cells	Licocoumarone, licoflavonol, glyasperin D and 2′‐methoxyisoliquiritigenin showed inhibition viral absorption, viral replication, and viral RNA synthesis	Kwon et al., 2010
Tylosema esculentum Burch.	Rotaviruses human (H4)	0.01 to 0.001 mg/ml	MA‐104 cells	Showed profound CPE and interfered with viral replication and strengthened the intestinal epithelial barrier function	Chingwaru et al., 2011
Quillaja saponaria	Rhesus rotavirus	0.015 and 0.0125 mg/mouse (p.o.)	Newborn Balb/c mice/MA104 cells	Alleviated rotavirus infection by coating target cells and hence reduce rotavirus induced diarrhea	Tam and Roner, 2011
Vaccinium macrocarpon (juice) and Vitis labrusca Linn. (juice)	SA‐11	50% concentration of juices in PBS	MA‐104 cells	Showed associated loss of RNA integrity of viral capsid protein	Lipson et al., 2011
Psidium guajava Linn.	SA‐11	0.027 ± 0.001 mg/ml, 0.027 ± 0.013 mg/ml, 1.350 ± 0.063 mg/ml and 2.7 ± 0.125 mg/ml	MA‐104 cells	Decreased the cell death in virus infected cells	Birdi et al., 2011
Nelumbo nucifera Gaertn. Aspalathus linearis, Urtica dioica Linn.Glycyrrhiza glabra Linn. and Olea europaea Linn.	SA‐11 and the Rhesus rotavirus Strain	IC50 < 300 μg/ml	MA‐104 cells	Exerted antiviral activities and has no positive effect on the maintenance of trans‐epithelial resistance	Knipping et al., 2012
Glycyrrhiza uralensis	Porcine rotavirus K85 (G5P[7]) Strain	100, 200, and 400 mg/ml (p.o.)	Colostrum deprived piglets/TF‐104 cells	Cured rotavirus diarrhea and down‐regulated proinflammatory cytokines and its related transcription factor and signaling molecules	Alfajaro et al., 2012
Proanthocyanidins (Vaccinium macrocarpon and Vitis labrusca)	SA‐11	1,000 μg/ml in PBS	MA‐104 cells	Proanthocyanidins effectively blocked capsid protein (VP6) binding to host cells	Lipson et al., 2012
Vaccinium macrocarpon and Vitis labrusca	SA‐11	50% concentrations of juices in PBS	MA‐104 cells	Cranberry juice was most effective at pH 2.7 and grape juice at a suspension pH of 6.7.	Cecílio et al., 2012
Alpinia katsumadai	Bovine G8P(7) and porcine G5P(7]) rotaviruses	EC50 0.7 ± 0.4 to 33.7 ± 6.5 μg/ml against G5P(7) strainEC50 8.4 ± 2.2μg/ml, 6.5 ± 0.8μg/ml, and 8.4 ± 5.0 μg/ml against G8P(7) strain	MA‐104 cells	Blocked viral adsorption	Kim et al., 2012
Achillea kellalensis Boiss.	Bovine rotavirus	EC50 100 μg/ml	MA‐104 cells	Prevented viral replication and inhibited the viral CPE	Taherkhani et al., 2013
Tannins (Diospyros kaki Linn.)	Viral strains	0.05%, 0.025% and 0.005% of tannins	MA‐104 cells	Inhibited attachment of the virus to the cells	Ueda et al., 2013
Rice bran (Oryza sativa Linn.)	Human rotavirus(VirHRV)Wa strain(G1P1A[8])	10% of the pigs total daily calorie	Neonatal gnotobotic pigs	Rice bran promoted thedevelopment of IFN‐T cell responses, total IgM IgSCs in ileum and spleen, total IgA IgSCs in spleen and blood, and total serum IgM, IgA, and IgG antibody production	Yang et al., 2014
Achyrocline bogotensis DC.	Rhesus rotavirus	Substances dissolved in DMSO to a 100 mg/ml; dilutions μg/ml 0–1.000 down	MA‐104 cells	Exhibited antirotaviral activity characterized by a virucidal effect and by the reduction of the infectious particles produced post‐infection	Taherkhani et al., 2015
Eucalyptus camaldulensis Dehnh. (essential oils)	Human rotavirus (Wa) strain	1/10 dilutions	MA‐104 cells	Reduced viral titres against rotavirus	El‐Baz et al., 2015
Achillea fragrantissima Linn. Nitraria retusa (Forssk.) Asch	Human rotavirus (Wa) strain	IC50 1.0–1.2 mg/ml and IC50 0.9–1.4 mg/ml	MA‐104 cells	Reduced viral titres against rotavirus	Mohamed et al., 2015
α‐Glucosyl hesperitin and epigallocatechin gallate	SA‐11	100 × 103 μg/ml nd 80, 160, and 320 μg/ml	MA‐104 cells	Loss of viral capsid protein	Huang et al., 2015
Genistein	Human rotavirus (Wa) and SA‐11 strain	>160 μM	MA‐104 human epithelial colorectal (Caco2) cells	Genistein inhibited rotavirus replication by upregulating AQP4 expression via the cAMP/PKA/CREB signaling pathway	Lipson et al., 2015
Resveratrol, Piceatannol, Trans‐arachidin‐1 and Transarachidin‐3	SA‐11	10–20 μM	Human adenocarcinoma intestinal cell lines (HT29 FT8) and MA‐104 cells	Two stilbenoids, trans‐arachidin‐1 and transarachidin‐3 showed therapeutic potential against rotavirus replication via downregulating NSP4 protein levels	Ball et al., 2015
Myracrodruon urundeuva	SA‐11	50–500 μg/ml	MA‐104 cells	Diminished the multiplication of the virus including inhibiting the CPE	Cecílio et al., 2016