Recent insights on anti-dengue virus (DENV) medicinal plants: review on in vitro, in vivo and in silico discoveries

Figures & data

Table 1. Summary of medicinal plants from around the world, their DENV inhibition activities and study approach, classified into type of experiments: (a) in vitro antiviral and cytotoxicity studies, (b) in vitro gene and/or protein expression studies, (c) in silico molecular docking studies, (d) animal studies, (e) human studies, and (f) isolation and structure analysis.

(a) In vitro antiviral and cytotoxicity studies.
Plant name	Parts of plants used	Targeted DENV serotype	Study parameters	References
Acacia catechu	Dried fruit (powder form)	DENV-1, -2, -3, -4	IC50 = 0.18 µg ml^−1	(Panya et al. 2019)
Acorus calamus	Not specifically mentioned	DENV-2	CC50 = 424.93 µg ml^−1; EC50 = n.d.	(Rosmalena et al. 2019)
	Roots		tatanan A on DENV2-induced cell toxicity with an EC50 = 3.9 µM	(Yao et al. 2018)
Alternanthera philoxeroides	Extracted from plant as mentioned in Chinese article in 1989 https://www.cnki.com.cn/Article/CJFD1989-ZGZY198908022.htm	DENV-2	TD50 = 47.43 to 106.06 based on type of extracts	(Jiang et al. 2005)
Anacolosa pervilleana	Leaves	DENV5 NS5 polymerase	IC50 = 3 µM	(Bourjot et al. 2012a)
Andrographis paniculatata	Purchased andrographolide	DENV-2, DENV-4	EC50 = 21.304 and 22.739 µM	(Panraksa et al. 2017)
Arrabidaea pulchra	Leaves	DENV-2	EC50 = 46.8 ± 1.6 µg/ml	(Brandão et al. 2013)
Azadarachta indica	Leaves	DENV-2	TCID50 = 100–10,000	(Parida et al. 2002)
Basilicum polystachyon	Not specifically mentioned	DENV serotype not mentioned	IC50 = 1.4 ± 2/1 µM	(Tan et al. 2019)
Boesenbergia rotunda	Rhizome	DENV-2 NS2B/3 protease	Ki = 21–377 µM based on compound	(Kiat et al. 2006)
Castanospermum australe	Seeds	DENV-1, -2, -3, -4	Huh-7 human hepatoma cell (IC50 = 85.7 µM), BHK-21 cells (IC50 = 1 µM)	(Whitby et al. 2005)
Chondrus crispus	Purchased carrageenans	DENV-2	EC50 of Vero cells ≥50 µg ml^−1, C6/36 HT cells = 1.3 µg ml^−1 respectively	(Laura B Talarico et al. 2011)
Cissampelos pareira	Aerial parts	DENV-1, -2, -3, -4	IC50 ≤ 25 µg ml^−1	(Sood et al. 2015)
Cladogynos orientalis	Whole plant	DENV-2	CC50 = 312 µg ml^−1	(Klawikkan et al. 2011)
Cladosiphon okamuranus	Pickled seaweed	DENV -2, -3, -4	IC50 = 4.7, 500 and 365 µg ml^−1	(Hidari et al. 2008)
Coptis chinensis	Purchased palmatine	DENV-2	EC50 = 26.4 µM	(F. Jia et al. 2010)
Cryptocarya chartacea	Trunk bark	DENV NS5 RNA-dependent RNA polymerase (RdRp)	IC50 = 1.8 to 4.2 µM	(P. Allard et al. 2011)
Cryptonemia crenulata	Not specifically mentioned	Selective inhibitors of DENV-2, DENV-3 and DENV-4, inactive against DENV-1	IC50 = DENV-2 (around 1 µg ml^−1), DENV-3 (13.9 – 14.2 µg ml^−1) and DENV-4 (29.3 to >50 µg ml^−1) respectively	(L.B. Talarico et al. 2005)
Curcuma longa	Not specifically mentioned – extract obtained from PT Konimex, Solo	DENV-2	CC50 of 85.4 µg ml^−1	(Ichsyani et al. 2017)
Cymbopogon citratus	Not specifically mentioned	DENV-2	CC50 = 183.74 and EC50 = 29.37 µg ml^−1	(Rosmalena et al. 2019)
Distictella elongata	Leaves, fruits, stems	DENV-2	EC50 of 11.1 ± 1.6 µg ml^−1	(Simoes et al. 2011)
Doratoxylon apetalum	Aerial parts	DENV-1, -2, -3, -4	IC50 = 96.35, 16.75, 25.90 and 23.30 µg ml^−1 for DENV1-4 respectively	(Haddad et al. 2019)
Flacourtia ramontchi	Stem bark	DENV RNA polymerase	IC50 = 0.85 ± 0.1 µM	(Bourjot et al. 2012b)
Flagellaria indica	Whole plant	DENV-2	CC50 = 312.5 µg ml^−1	(Klawikkan et al. 2011)
Ficus septica	Fruit, heartwood, leaves, stem	DENV-1 and DENV-2	IC50 = 3.05 – >100 µg ml^−1	(Huang et al. 2017)
Gastrodia elata	WSS45, a sulfate derivative of a novel a-D-glucan extracted from Gastrodia elata Bl	DENV-2	EC50 =  0.68 ± 0.17 µg ml^−1	(Tong et al. 2010)
Gymnogongrus griffithsiae	Not specifically mentioned	Selective inhibitors of DENV-2, DENV-3 and DENV-4, inactive against DENV-1	IC50 = DENV-2 (around 1 µg ml^−1), DENV-3 (13.9 – 14.2 µg ml^−1) and DENV-4 (29.3 - >50 µg ml^−1) respectively	(L.B. Talarico et al. 2005)
Gymnogongrus torulosus	Milled seaweed	DENV-2	IC50 = 0.19–1.7 µg ml^−1	(Pujol et al. 2002)
Hedyotis auricularia	Leaves, stems, roots	DENV-2 NS2B-NS3pro	IC50 ≤ 100 µg ml^−1	(Rothan et al. 2014)
Hemigraphis reptans
Hippophae rhamnoides	Leaves	DENV-2	decrease TNF-α, increase IFN-γ, decrease viral titer significantly (p < 0.01)	(Jain et al. 2008)
Houttuynia cordata	Whole plant	DENV-2	CC50 = 312.5 µg ml^−1	(Klawikkan et al. 2011)
Kaempferia parviflora	Leaves, stems	DENV-2	–	(Sarangi and Padhi 2014; Kanna and Krishnakumar 2019)
Leucaena leucocephala	Seeds	DENV-1	37 mg L^−1 caused 100-fold decrease in virus titer of DENV-1 infected C6/36 cells	(Ono et al. 2003)
Laurentia longiflora	Leaves, stems, roots	DENV-2 NS2B-NS3pro	IC50 ≤ 100 µg ml^−1	(Rothan et al. 2014)
Mimosa scabrella	Seeds	DENV-1	347 mg L^−1 caused 100-fold decrease in virus titer of DENV-1 infected C6/36 cells	(Ono et al. 2003)
Momordica charantia	Roots, entire fruit	DENV-1	MNTD = 0.20 mg.ml^−1	(Tang et al. 2012)
Myristica fatua	Not specifically mentioned	DENV-2	CC50 = 474.42; EC50 = 25.33 µg ml^−1	(Rosmalena et al. 2019)
Myrtopsis corymbosa	Leaves, bark	DENV2 RNA dependent RNA polymerase (DENV-NS5 RdRp)	Inhibition at 1 µg ml^−1 for leaves extract: 20, 64, 50% and strongest inhibition by bark extract: 33, 68, 87%	(Coulerie et al. 2013)
Nephelium lappaceum	Rind	DENV-2	IC50 = 1.75 µM; ELISA competitive binding assay confirmed geraniin’s interaction with rE-DIII with high affinity	(Ahmad et al. 2017)
Ocimum sanctum	Whole aerial body	DENV-1	MNTD = 23.44 µg ml^−1; PFU/ML = 157.5 ± 67.6	(Ling et al. 2014)
Pavetta tomentosa	Leaves	DENV-2	CC50 = 11.45%	(Pratheeba et al. 2019)
Phyllanthus amarus, Phyllanthus niruri, Phyllanthus urinaria and Phyllanthus watsonii	Whole plant except roots	DENV-2	MNTD = aqueous and methanolic extracts = 250.0 µg ml^−1 and 15.63 µg ml^−1 respectively	(S.H. Lee et al. 2013)
Piper retrofractum	Whole plant	DENV-2	CC50 = 625 or 156.25 µg ml^−1 for ethanol or dichloromethane extract respectively	(Klawikkan et al. 2011)
Psidium guajava	Bark	DENV-2	CC50 = 1000.0; EC50 = 7.8	(Trujillo-correa et al. 2019)
Quercus lusitanica	Seeds	DENV-2	0.032 mg ml^−1 to 180 µg ml^−1 of Quercus lusitanica methanol extracts completely inhibit the dengue virus infection at TCID50 of 1–1000	(Muliawan et al. 2006; N.A. Rahman et al. 2006)
Rhizophora apiculata	Whole plant	DENV-2	CC50 = 625 µg ml^−1	(Klawikkan et al. 2011)
Schisandra chinensis	Purchased compounds	DENV-1, -2, -3, -4	EC50 = 28.1 ± 0.42 µM	(Yu et al. 2017)
Scutellaria baicalensis	Roots	DENV-2	IC50 = 1.55 µg ml^−1; qRT-PCR results = 12.5 µg/mL and 25 µg/mL of baicalein decreased the DENV-2 RNA production 69.2 ± 1.6 and >90% respectively	(Zandi et al. 2012)
Senna angustifolia	Leaves, stems, roots	DENV-2 NS2B-NS3pro	IC50 = 30.1 µg ml^−1; qRT-PCR = (67.2% ± 6.3)	(Rothan et al. 2014)
Tarenna asiatica	Leaves	DENV serotype not mentioned	CC50 = 34.35%	(Pratheeba et al. 2019)
Tephrosia madrensis	Not specifically mentioned	DENV-2	EC50 = 25 µM glabranine;12 and 25 µM 7-O-methyl-glabranine reduced intracellular virus replication by 76.9% and 75% respectively	(Sánchez et al. 2000)
Tridax procumbens	Leaves, stems, roots	DENV-2 NS2B-NS3pro	IC50 = 25.6 µg ml^−1; qRT-PCR = (86.3% ± 2.7)	(Rothan et al. 2014)
Trigonostemon cherrieri	Bark, wood	DENV polymerase	IC50 = 12.7, 3.1 and 16 µM	(P. Allard et al. 2012)
Uncaria tomentosa	Stem barks	inhibited cytokine activities, reduced TNF-α, IL-10, IFN-α production levels	IL-10 levels in DENV-2 infected human monocytes lowered to 244 ± 60 pg ml^−1	(Reis et al. 2008)
Vernonia cinerea	Leaves, stems, roots	DENV-2 NS2B-NS3pro	IC50 = 23.7 µg ml^−1 qRT-PCR = (79.5% ± 4.3)	(Rothan et al. 2014)
Zostera marina	Designed and provided by CernoFina, LLC (Portland, ME)	DENV-1, -2, -3, -4	ZA showed IC50 = 2.3 mM	(Rees et al. 2008)
*The data shown are mean ± S.D., CC50 = 50% cytotoxic concentration, EC50 = concentration of a drug that gives half-maximal response, IC50 = half maximal inhibitory concentration, Ki = inhibitory constant, MNTD = maximal non-toxic dose, TCID50 = tissue culture infective dose 50%, TD50 = the dose of drug that causes a toxic response in 50% of the population.
(b) In vitro gene and/or protein expression studies
Plant name	Parts of plants used	Targeted DENV serotype	Study parameters	References
Allium sativum.	Purchased organosulfur garlic compounds	DENV-2	Inducible nitric oxide synthase (iNOS) levels reduced	(Hall et al. 2017)
Garcinia mangostana	Pericarp	DENV-1, -2, -3, -4	Reduced all cytokine/chemokine transcription (p < 0.001)	(Tarasuk et al. 2017)
Lonicera japonica	Flower buds	DENV-2	NS1 RNA expression reduction by 27%, NS1 protein expression by 52%	(Y.-R. Lee et al. 2017)
Norantea brasiliensis	Leaves	DENV-2	downregulated TNF-α, IL-6, IL-10 and IFN-α secretion, cellular antigenic viral load and secreted NS1 protein reduction	(Fialho et al. 2016)
Phyllanthus amarus, Phyllanthus niruri, Phyllanthus urinaria and Phyllanthus watsonii	Whole plant except roots	DENV-2	24 proteins were deemed significantly altered expression	(S.H. Lee et al. 2013)
Schisandra chinensis	Purchased compounds	DENV-1, -2, -3, -4	schisandrin A exerts inductive activity of antiviral IFN-I gene expression	(Yu et al. 2017)
(c) In silico molecular docking studies
Plant name	Parts of plants used	Targeted DENV serotype	Measured parameters	References
Acorus calamus	Not mentioned	DENV-2		(Rosmalena et al. 2019)
Boesenbergia rotunda	Finger root	DENV-2	Competitive inhibition towards DENV-2 NS2B/NS3, estimated Ki are 9.1 µM to 21 µM	(Frimayanti et al. 2012)
Cladosiphon okamuranus	Pickled seaweed	DENV -2, -3, -4	-	(Hidari et al. 2008)
Cymbopogon citratus	Not specifically mentioned	DENV-2	-	(Rosmalena et al. 2019)
Glycyrrhiza glabra	Not specifically mentioned – 2194 plant-derived secondary metabolites	DENV protease	-	(Powers and Setzer 2016)
Myristica fatua	Not specifically mentioned	DENV-2	-	(Rosmalena et al. 2019)
Nephelium lappaceum	Rind	DENV-2	geraniin binds to DENV E protein, specifically at the DIII region	(Ahmad et al. 2017)
Psidium guajava	Bark	DENV-2	-	(Trujillo-correa et al. 2019)
*The data shown are mean ± S.D., Ki = inhibitory constant.
(d) Animal studies
Plant name	Parts of plants used	Targeted DENV serotype	Measured parameters	References
Azadarachta indica	Leaves	DENV-2	Inhibited DENV at non-toxic doses in the range of 120–30 mg/ml	(Parida et al. 2002)
Carica papaya	Leaves	DENV-2	Increase in plasma cytokines in DENV infected AG129 mice treated with 500 and 1000 mg Kg^−1 freeze-dried Carica Papaya leaf juice	(Norahmad et al. 2019)
			Decrease envelope and NS1 protein expression in DENV infected THP-1 cells, decrease in erythrocyte damage	(Sharma et al. 2019)
Castanospermum australe	Seeds	DENV-1, -2, -3, -4	0.2, 1, 5 mg of castanospermine gives survival rates of 25%, 90% and 85% in mice	(Whitby et al. 2005)
Cissampelos pareira	Aerial parts	DENV-1, -2, -3, -4	No visible effect on platelet counts or erythrocyte viability	(Sood et al. 2015)
Curcuma longa	Not specifically mentioned – extract obtained from PT Konimex, Solo	DENV-2	DENV-2 virus titer decreased at the level of 3.6  ×  10^3 FFU ML^−1 at 24 h after infection	(Ichsyani et al. 2017)
Leucaena leucocephala	Seeds	DENV-1	at dosage of 49 mg Kg^−1, protected mice against death at 96.5%	(Ono et al. 2003)
Lonicera japonica	Flower buds	DENV-2	reduction of over 30% virus titer in infected mice brain tissue	(Y.-R. Lee et al. 2017)
Mimosa scabrella	Seeds	DENV-1	at dosage of 49 mg Kg^−1 protected mice against death at 87.7%	(Ono et al. 2003)
*The data shown are mean ± S.D., focus forming units per milliliter = FFU ML^−1.
(e) Human studies
Plant name	Parts of plants used	Targeted DENV serotype	Measured parameters	References
Boerhaavia diffusia	plant of Boerhaavia diffusia in 10gm	DENV serotype not mentioned	-	(Bharati and Sinha 2012)
Euphorbia hirta	Plant parts not specifically mentioned – herbal water	DENV serotype not mentioned	Total Leukocyte Count significantly increased ranging from 4000 to 11,000 mm^3 in both males and females	(Mir et al. 2012)
Lonicera japonica	Flower buds	DENV-2	Upregulated miRNAs – let-7a showed highest expression level	(Y.-R. Lee et al. 2017)
(f) Isolation and Structure analysis
Plant name	Parts of plants used	Targeted DENV serotype	Measured parameters	Study approach	References
Isatis tinctoria	Whole plant	GB-7 isolated had potential against DENV-2, but not tested yet	Isolated 27 compounds from aerial parts of Isatis tinctoria for later experiments	Spectrum analysis	(Gao et al. 2018)

Table 2. Essential oils from medicinal plants showing pronounced virucidal activity.

	Cytotoxicity and Inhibitory Activity
Essential Oil from Plant	CC50	IC50	VC50	Selectivity index: CC50/IC50	References
Artemisia douglasiana	313 ppm	–	60 ppm	–	(C.C. García et al. 2003)
Eupatorium patens	294 ppm	–	150 ppm	–	(C.C. García et al. 2003)
Lantana grisebachii	>500 ppm	21.1 ppm	–	>23.7	(Cybele C. García et al. 2010)
Lippia alba	139.5 µg ml^−1	0.4 µg ml^−1	–	349	(Ocazionez et al. 2010)

*CC₅₀ = 50% cytotoxic concentration, IC₅₀ = half maximal inhibitory concentration, ppm = parts per million, VC₅₀ = concentration required to inactivate virions by 50%.

Table 3. Plant compounds and their respective DENV targets in silico.

DENV Target	Compounds	Plant name	References
DENV envelope protein (E protein)	Fucoidan	Cladosiphon okamuranus	(Hidari et al. 2008)
	2,3-Dehydrosilybin, 3′,5,7-Trihydroxy-4′-methoxy-5-,6-diprenylisoflavanone, 3′-O-Methyldiplacone, 4′-O-Methyldiplacone, 8β-[4-Hydroxy-5-(5-hydroxytigloyloxy)-tigloyl]santamarin, 8-Prenylmucronulatol, Angusticornin B, Betulafolienetriol, Bonannione A, Caffeoyl-p-coumaroyltartaric acid, Calebin A, Cannflavin A, Chandalone, Cisilandrin, Curcumin I, Diplacone, Furost-20(22)-ene-2,3,26-triol, Hispaglabridin A, Isosilybin A, Isosilybin B, Isosilybin C, Isosilybin D, Kanzonol Y, Paratocarpin L, Phyllanone B, Piperaduncin A, Rhinacanthin K, Silandrin A, Silandrin B, Silybin, Terrestriamide and Tuberine	Silybum marianum, Paulownia tomentosa, Cannabis sativa	(Powers and Setzer 2016)
	geraniin	Nephelium lappaceum	(Ahmad et al. 2017)
	Naringin and hesperidin	Psidium guajava	(Trujillo-correa et al. 2019)
DENV methyltransferase	8β–[4-Hydroxy-5-(5-hydroxytigloyloxy)tigloyl]santamarin, Acteol-26-ketone, Chartaceone B4, Curcumin I, Diplacone, Exiguaflavanone A, Flinderole B, Glabraisoflavanone B, Isoborreverine, Neosilyhermin A, Neosilyhermin B, Styracifolin B and Tubulosine	Glycyrrhia glabra, Curcuma longa	(Powers and Setzer 2016)
DENV RNA-dependent RNA polymerase (RdRp)	4,6-Dibenzoyl-2-[phenylhydroxymethyl]-3(2H)-benzofuranone, Dimethylisoborreverine, Drummondin E, Flinderole A, Flinderole B, Kanzonol Y, Neosilyhermin B and Pungiolide A	Glycyrrhia glabra	(Powers and Setzer 2016)
DENV NS2B-NS3 protease	4-hydroxyoanduratin, panduratin A and synthetic inhibitor called 246DA	Boesenbergia rotunda	(Frimayanti et al. 2012)
	Quercetin	Carica papaya	(Senthilvel et al. 2013)
	(-)-Gossypol, mangostenone C, garcidepsidone A, 4-hydroxyacetophenone 4-O-(6′-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside, demethylcalabaxanthone, mangostanin	Gossypium hirsutum, Garcinia mangostana, Garcinia parvifolia, Salvia officinalis, Garcinia vieillardii	(T. ul Qamar et al. 2014)
	nimbin, desacetylnimbin and desacetylsalannin	Azadirachta indica	(Dwivedi et al. 2016)
	2′,3,4,4′,6,-Pentamethoxychalcone, 3,3′,4,5′-Tetrahydroxy-5-prenylbibenzyl, 3,3′,5′-trihydroxy-4-methoxy-5-prenylbibenzyl, 3,4-Dehydro-5-carboxystrictosidine (aglycone), 3-Acetoxy-4′,5-dihydroxy-3′-prenyldihydrostilbene, 4′-O-Methylglycyrrhisoflavone, 4′-O-Methylneobavaisoflavone, 8-Prenylmucronulatol, agnuside (aglycone), balsacone A, balsacone B, balsacone C, chartaceone A2, euchrestaflavanone A, flemiflavanone D, glycyrrhisoflavone, isosilandrin A, kanzonol Y, licobenzo furan, nishindaside (aglycone), rhodiolin, silyhermin, solophenol D and umbelliprenin,	Flemingia stricta, Glycyrrhiza glabra, Macaranga pleiostemona, and Populus balsamifera	(Powers and Setzer 2016)
	uncinanone B, 5-hydroxybowdichione, prunectin, 5,7,3′,4′-tetrahydroxyisoflavone, alpunumisoflavone and glicoisoflavone	Desmodium uncinatum, Dalbergia candenatensis, Glycine max, Calophyllum polyanthum, Ficus microcarpa and Glycyrrhiza uralensis	(M.T.U. Qamar et al. 2017)
	Ligand 18 and 21	D0713 bearing thioguanine scaffold	(Hariono et al. 2019)
DENV NS3 helicase	1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one, 3′-O-Methyldiplacol, 3′-O-Methyldiplacone, 4,6-Dibenzoyl-2-[phenylhydroxymethylene]-3(2H)-benzofuranone, angusticornin B, balsacone A, balsacone C, caffeoyl-p-coumaroyltartaric acid, charteceone B3, chicoric acid, cimicifugic acid B, cimicifugic acid G, cimiciphenol, cimiracemate D, curcumin I, curcumin II, curcumin III, dihydrocurcumin and mulberrofuran Y	black cohosh (Cimiciguga racemosa), Curcuma longa	(Powers and Setzer 2016)
DENV-2 NS5	geraniol, geranial and geranyl acetate	Cymbopogon citratus	(Rosmalena et al. 2019)
	β-asarone, acoric acid, calamusin D	Acorus calamus	(Rosmalena et al. 2019)
	artesunic aicd, homoegonol, myristicin	Myristica fatua	(Rosmalena et al. 2019)
	quercetin, catechin, naringin, hesperidin	Psidium guajava	(Trujillo-correa et al. 2019)
NS4B	silymarin, flavobion, derrisin, isosilybin, mundulinol, silydianin, isopomiferin, narlumicine and oxysanguinarine	Silybum marianum, Tanacetum parthenium, Fumaria indica, Solanum nigrum, Andrographis paniculata, and Melissa officinalis	(Qaddir et al. 2017)
	catechin, cianidanol, epicatechin, eupatoretin, glabranin, laurifolin, DL-catehin	Green tea, woody plants	(Paul et al. 2016)
NS1, NS3 and NS5	canthin-6-one 9-O-beta-glucopyranoside, kushenol W and kushenol K	Eurycoma harmandiana, Sophora flavescens	(M.T.U. Qamar et al. 2019)

Figure 1. (a) DENV is transmitted into the human body via infected Aedes mosquito. DENV attack the immune system leading to ‘cytokine storm’ and vascular leakage. (b) Action of medicinal plants in regulating host immune response during DENV infection. Phytochemicals targeting DENV entry and cytokines producing factors, during DENV infection are responsible to inhibit cytokines production, increase anti-viral IFN-γ and platelet production, thus dampens the cytokine storm and prevent vascular leakage.

Figure 1. Continued.

Figure 2. Overview of the DENV structural and non-structural proteins and the proposed potential target sites (e.g. NS2b/NS3) for DENV inhibition by phytochemicals.

Panya A, Yongpitakwattana P, Budchart P, Sawasdee N, Krobthong S, Paemanee A, Roytrakul S, Rattanabunyong S, Choowongkomon K, Yenchitsomanus P. 2019. Novel bioactive peptides demonstrating anti-dengue virus activity isolated from the Asian medicinal plant Acacia catechu. Chem Biol Drug Des. 93(May 2018):100–109.

 Google Scholar

Rosmalena R, Elya B, Dewi BE, Fithriyah F, Desti H, Angelina M, Hanafi M, Lotulung PD, Prasasty VD, Seto D. 2019. The antiviral effect of Indonesian medicinal plant extracts against dengue virus In vitro and In silico. Pathogens. 8(85):1–11.

 Google Scholar

Yao X, Ling Y, Guo S, Wu W, He S, Zhang Q, Zou M, Nandakumar KS, Chen X, Liu S. 2018. Tatanan A from the acorus calamus L. Root inhibited dengue virus proliferation and infections. Phytomedicine. 42:258–267.

 Web of Science ®Google Scholar

Jiang W, Luo X, Kuang S. 2005. Effects of alternanthera philoxeroides griseb against dengue virus in vitro. J First Military Med Univ. 25(4):454–456.

 Google Scholar

Bourjot M, Leyssen P, Eydoux C, Guillemot J, Canard B, Rasoanaivo P, Guéritte F, Litaudon M. 2012a. Chemical constituents of anacolosa pervilleana and their antiviral activities. Fitoterapia. 83:1076–1080. doi:10.1016/j.fitote.2012.05.004.

 PubMed Web of Science ®Google Scholar

Panraksa P, Ramphan S, Khongwichit S, Smith DR. 2017. Activity of andrographolide against dengue virus. Antiviral Res. 139:69–78.

 Web of Science ®Google Scholar

Brandão GC, Kroon EG, Souza DER, Filho JDS, Oliveira AB. 2013. Chemistry and antiviral activity of arrabidaea pulchra (bignoniaceae). Molec. 18:9919–9932.

 PubMed Web of Science ®Google Scholar

Parida MM, Upadhyay C, Pandya G, Jana AM. 2002. Inhibitory potential of neem (azadirachta indica juss) leaves on dengue virus type-2 replication. J Ethnopharmacol. 79:273–278.

 PubMed Web of Science ®Google Scholar

Tan YP, Houston SD, Modhiran N, Savchenko AI, Boyle GM, Young PR, Watterson D, Williams CM. 2019. Stachyonic acid: a dengue virus inhibitor from basilicum polystachyon. Chem European J. 25:5664–5667.

 Web of Science ®Google Scholar

Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Rahman NA. 2006. Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of fingerroot, boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease. Bioorg Med Chem Lett. 16(12):3337–3340.

 PubMed Web of Science ®Google Scholar

Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. 2005. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 79(14):8698–8706.

 PubMed Web of Science ®Google Scholar

Talarico LB, Noseda MD, Ducatti DRB, Duarte MER, Damonte EB. 2011. Differential inhibition of dengue virus infection in mammalian and mosquito cells by iota-carrageenan. J Gen Virol. 92:1332–1342.

 PubMed Web of Science ®Google Scholar

Sood R, Raut R, Tyagi P, Kumar P. 2015. Cissampelos pareira linn: natural source of potent antiviral activity against all four dengue virus serotypes. PLoS Negl Trop Dis. 9(12):e0004255.

 PubMed Web of Science ®Google Scholar

Klawikkan N, Nukoolkarn V, Jirakanjanakit N, Yoksan S, Wiwat C, Thirapanmethee K. 2011. Effect of Thai medicinal plant extracts against dengue virus in vitro. Original Article Mahidol Univ J Pharmac Sci. 38(1–2):13–18.

 Google Scholar

Hidari KIPJ, Takahashi N, Arihara M, Nagaoka M, Morita K, Suzuki T. 2008. Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem Biophys Res Commun. 376:91–95.

 PubMed Web of Science ®Google Scholar

Jia F, Zou G, Fan J, Yuan Z. 2010. Identification of palmatine as an inhibitor of west Nile virus. Arch Virol. 155:1325–1329.

 PubMed Web of Science ®Google Scholar

Allard P, Dau ETH, Eydoux C, Guillemot J-C, Dumontet V, Poullain C, Canard B, Gueritte F, Litaudon M. 2011. Alkylated flavanones from the bark of cryptocarya chartacea as dengue virus NS5 polymerase inhibitors. J Nat Prod. 74:2446–2453.

 PubMed Web of Science ®Google Scholar

Talarico LB, Pujol CA, Zibetti RGM, Faria PCS, Noseda MD, Duarte MER, Damonte EB. 2005. The antiviral activity of sulfated polysaccharides against dengue virus Is dependent on virus serotype and host cell. Antiviral Res. 66:103–110.

 PubMed Web of Science ®Google Scholar

Ichsyani M, Ridhanya A, Risanti M, Desti H, Ceria R, Putri DH, Sudiro TM, Dewi BE. 2017. Antiviral effects of Curcuma longa L. against dengue virus in vitro and in vivo. IOP Conf Series: Earth and Environ Sci Paper. 101:1–10. Available from: https://iopscience.iop.org/article/10.1088/1755-1315/140/1/012115/meta.

 Google Scholar

Simoes L, Maciel G, Brandao G, Kroon E, Castilho R, Oliveira A. 2011. Antiviral activity of distictella elongata (vahl) urb. (bignoniaceae), a potentially useful source of anti-dengue drugs from the state of minas gerais, Brazil. Lett Appl Microbiol. 53:602–607.

 Web of Science ®Google Scholar

Haddad JG, Koishi AC, Gaudry A, dos Santos CND, Viranaicken W, Desprès P, El Kalamouni C. 2019. Doratoxylon apetalum, an indigenous medicinal plant from mascarene islands, is a potent inhibitor of zika and dengue virus infection in human cells. Int J Mol Sci. 20(2382):1–13.

 Google Scholar

Bourjot M, Leyssen P, Eydoux C, Guillemot JC, Canard B, Rasoanaivo P, Guéritte F, Litaudon M. 2012b. Flacourtosides A-F, phenolic glycosides isolated from flacourtia ramontchi. J Nat Prod. 75(4):752–758.

 PubMed Web of Science ®Google Scholar

Huang N-C, Hung W-T, Tsai W-L, Lai F-Y, Lin Y-S, Huang M-S, Chen J-J, Lin W-Y, Weng J-R, Chang T-H. 2017. Ficus septica plant extracts for treating dengue virus in vitro. PeerJ. 2017(5):e3448.

 Google Scholar

Tong XK, Qiu H, Zhang X, Shi LP, Wang GF, Ji FH, Ding HY, Tang W, Ding K, Zuo JP. 2010. WSS45, a sulfated α-D-glucan, strongly interferes with dengue 2 virus infection in vitro. Acta Pharmacol Sin. 31:585–592.

 PubMed Web of Science ®Google Scholar

Pujol CA, Estevez JM, Carlucci MJ, Ciancia M, Cerezo AS, Damonte EB. 2002. Novel DL-galactan hybrids from the red seaweed gymnogongrus torulosus are potent inhibitors of herpes simplex virus and dengue virus. Antiviral Chem Chemother. 13:83–89.

 Google Scholar

Rothan H, Zulqarnain M, Ammar Y, Tan E, Rahman N, Yusof R. 2014. Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay. Trop Biomed. 31(2):286–296.

 PubMed Web of Science ®Google Scholar

Jain M, Ganju L, Katiyal A, Padwad Y, Mishra KP, Chanda S, Karan D, Yogendra KMS, Sawhney RC. 2008. Effect of hippophae rhamnoides leaf extract against dengue virus infection in human blood-derived macrophages. Phytomedicine. 15:793–799.

 PubMed Web of Science ®Google Scholar

Sarangi MK, Padhi S. 2014. Dengue and its phytotherapy: a review. Int J Pharmac Phytopharmacol Res. 4(1):37–46.

 Google Scholar

Kanna SU, Krishnakumar N. 2019. Anti-Dengue medicinal plants: a mini review. J Pharmacogn Phytochem. 8(3):4245–4249.

 Google Scholar

Ono L, Wollinger W, Rocco IM, Coimbra TLM, Gorin PAJ, Sierakowski M. 2003. In vitro and in vivo antiviral properties of sulfated galactomannans against yellow fever virus (BeH111 strain) and dengue 1 virus (hawaii strain). Antiviral Res. 60:201–208.

 Web of Science ®Google Scholar

Tang LIC, Ling APK, Koh RY, Chye SM, Voon KGL. 2012. Screening of anti-dengue activity in methanolic extracts of medicinal plants. BMC Complement Altern Med. 12(3):1–10. Available from: https://www.biomedcentral.com/1472-6882/12/3.

 Google Scholar

Coulerie P, Maciuk A, Lebouvier N, Hnawia E, Guillemot JC, Canard B, Figadère B, Nour M. 2013. Phytochemical study of myrtopsis corymbosa, perspectives for anti-dengue natural compound research. Rec Nat Prod. 7(3):250–253.

 Google Scholar

Ahmad SAA, Palanisamy UD, Tejo BA, Chew MF, Tham HW, Hassan SS. 2017. Geraniin extracted from the rind of nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication. Virol J. 14(229):1–13.

 Google Scholar

Ling APK, Khoo BF, Seah CH, Foo KY, Cheah RK, Chye SM, Koh RY. 2014. Inhibitory activities of methanol extracts of andrographis paniculata and ocimum sanctum against dengue – 1 virus. International conference on biological, environment and food engineering, August 4–5, p. 47–52.

 Google Scholar

Pratheeba T, Taranath V, Sai Gopal DVR, Natarajan D. 2019. Antidengue potential of leaf extracts of pavetta tomentosa and tarenna asiatica (rubiaceae) against dengue virus and its vector aedes aegypti (diptera: culicidae). Heliyon. 5:e02732. doi:10.1016/j.heliyon.2019.e02732.

 Web of Science ®Google Scholar

Lee SH, Tang YQ, Rathkrishnan A, Wang SM, Ong KC, Manikam R, Payne BJ, Jaganath IB, Sekaran SD. 2013. Effects of cocktail of four local Malaysian medicinal plants (Phyllanthus Spp.) against dengue virus 2. BMC Complement Altern Med. 13(192):1–13.

 Google Scholar

Trujillo-correa AI, Quintero-gil DC, Diaz-castillo F, Quiñones W, Robledo SM, Martinez-gutierrez M. 2019. In vitro and in silico anti-dengue activity of compounds obtained from psidium guajava through bioprospecting. BMC Complement Altern Med. 19(298):1–16.

 Google Scholar

Muliawan SY, Kit LS, Devi S, Hashim O, Yusof R. 2006. Inhibitory potential of quercus lusitanica extract on dengue virus type 2 replication. Southeast Asian J Trop Med Public Health. 37:132–135.

 Google Scholar

Rahman NA, Hadinur SM, Rashid NN, Muhamad M, Yusof R. 2006. Studies on quercus iusitanica extracts on DENV-2 replication. Dengue Bulletin. 30:260–269.

 Google Scholar

Yu J, Wu Y, Tseng C, Lin C, Hsu Y, Chen Y-H, Lee J-C. 2017. Schisandrin A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway. Sci Rep. 7(45171):1–12. doi:10.1038/srep45171.

 Google Scholar

Zandi K, Teoh B, Sam S, Wong P, Mustafa MR, Abubakar S. 2012. Novel antiviral activity of baicalein against dengue virus. BMC Complement Altern Med. 12(214):1–9. BMC Complementary and Alternative Medicine.

 Google Scholar

Sánchez I, Gómez-Garibay F, Taboada J, Ruiz BH. 2000. Antiviral effect of flavonoids on the dengue virus. Phytother Res. 14:89–92.

 PubMed Web of Science ®Google Scholar

Allard P, Leyssen P, Martin M, Bourjot M, Dumontet V, Eydoux C, Guillemot J, et al. 2012. Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of trigonostemon cherrieri. Phytochemistry. 84:160–168. doi:10.1016/j.phytochem.2012.07.023.

 PubMed Web of Science ®Google Scholar

Reis SRIN, Valente LMM, Sampaio AL, Siani AC, Gandini M, Azeredo EL, D’Avila LA, Mazzei JL, Henriques MdGM, Kubelka CF. 2008. Immunomodulating and antiviral activities of uncaria tomentosa on human monocytes infected with dengue virus-2. Int Immunopharmacol. 8:468–476.

 PubMed Web of Science ®Google Scholar

Rees CR, Costin JM, Fink RC, Mcmichael M, Fontaine KA, Isern S, Michael SF. 2008. In vitro inhibition of dengue virus entry by p-sulfoxy-cinnamic acid and structurally related combinatorial chemistries. Antiviral Res. 80:135–142.

 PubMed Web of Science ®Google Scholar

Hall A, Troupin A, Londono-Renteria B, Colpitts TM. 2017. Garlic organosulfur compounds reduce inflammation and oxidative stress during dengue virus infection. Viruses. 9(159):1–10.

 Google Scholar

Tarasuk M, Songprakhon P, Chimma P, Sratongno P, Na-Bangchang K, Yenchitsomanus P. 2017. Alpha-Mangostin inhibits both dengue virus production and cytokine/chemokine expression. Virus Res. 240:180–189.

 PubMed Web of Science ®Google Scholar

Lee Y-R, Yeh S-F, Ruan X-M, Zhang H, Hsu S-D, Huang H-D, Hsieh C-C, et al. 2017. Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis. J Ethnopharmacol. 198:109–121. doi:10.1016/j.jep.2016.12.049.

 PubMed Web of Science ®Google Scholar

Fialho LG, da Silva VP, Regina S, Reis NI, Azeredo EL, Kaplan MAC, Figueiredo MR, Kubelka CF. 2016. Antiviral and immunomodulatory effects of norantea brasiliensis choisy on dengue virus-2. Intervirology. 59:217–227.

 Web of Science ®Google Scholar

Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Rahman NA. 2012. Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibitors from the components of fingerroot (boesenbergia rotunda). In Silico Biol. 11:29–37.

 Google Scholar

Powers CN, Setzer WN. 2016. An In-silico investigation of phytochemicals as antiviral agents against dengue fever. Comb Chem High Throughput Screening. 19(7):516–536.

 PubMed Web of Science ®Google Scholar

Norahmad NA, Mohd Abd Razak MR, Mohmad Misnan N, Md Jelas NH, Sastu UR, Muhammad A, Ho TCD, et al. 2019. Effect of freeze-dried carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice. BMC Complement Altern Med. 19(1):1–10.

 Google Scholar

Sharma N, Mishra KP, Chanda S, Bhardwaj V, Tanwar H, Ganju L, Kumar B, Singh SB. 2019. Evaluation of anti-dengue activity of carica papaya aqueous leaf extract and its role in platelet augmentation. Arch Virol. 164:1095–1110. doi:10.1007/s00705-019-04179-z.

 PubMed Web of Science ®Google Scholar

Bharati P, Sinha R. 2012. Study the effect of tinospora cardifolia (wild) miers and boerhaavia diffusia linn on dengue. Int J Ayur Herbal Med. 2(3):574–577.

 Google Scholar

Mir M, Khurshid R, Aftab R. 2012. Management of thrombocytopenia and flu-like symptoms in dengue patients with herbal water of euphorbia hirta. J Ayub Med College, Abbottabad: JAMC. 24(3–4):6–9.

 Google Scholar

Gao B, Zhang J, Xie L. 2018. Structure analysis of effective chemical compounds against dengue viruses isolated from isatis tinctoria. Canadian J Infect Disease Med Microbiol. 2018(Article ID 3217473):1–11.

 Google Scholar

García CC, Talarico L, Almeida N, Colombres S, Duschatzky C, Damonte EB. 2003. Virucidal activity of essential oils from aromatic plants of San Luis, Argentina. Phytother Res. 17:1073–1075.

 PubMed Web of Science ®Google Scholar

García CC, Acosta EG, Carro AC, Belmonte MCF, Bomben R, Duschatzky CB, Perotti M, Schuff C, Damonte EB. 2010. Virucidal activity and chemical composition of essential oils from aromatic plants of central west Argentina. Nat Prod Commun. 5(8):1307–1310.

 PubMed Web of Science ®Google Scholar

Ocazionez RE, Meneses R, Torres FÁ, Stashenko E. 2010. Virucidal activity of Colombian lippia essential oils on dengue virus replication in vitro. Memórias Do Instituto Oswaldo Cruz. 105(3):304–309.

 Web of Science ®Google Scholar

Senthilvel P, Lavanya P, Kumar KM, Swetha R, Anitha P, Bag S, Sarveswari S, Vijayakumar V, Ramaiah S, Anbarasu A. 2013. Flavonoid from carica papaya inhibits NS2B-NS3 protease and prevents dengue 2 viral assembly. Bioinformation. 9(18):889–895.

 PubMedGoogle Scholar

Qamar Tu, Mumtaz A, Ashfaq UA, Azhar S, Fatima T, Hassan M, Hussain SS, Akram W, Idrees S. 2014. Computer aided screening of phytochemicals from garcinia against the dengue NS2B/NS3 protease. Bioinformation. 10(3):115–118.

 Google Scholar

Dwivedi VD, Tripathi IP, Mishra SK. 2016. In silico evaluation of inhibitory potential of triterpenoids from azadirachta indica against therapeutic target of dengue virus, NS2B-NS3 protease. J Vec Borne Disease. 53(June 2016):156–161.

 Google Scholar

Qamar MTU, Ashfaq UA, Tusleem K, Mumtaz A, Tariq Q, Goheer A, Ahmed B. 2017. In-silico identification and evaluation of plant flavonoids as dengue NS2B/NS3 protease inhibitors using molecular docking and simulation approach. Pak J Pharm Sci. 30(6):2119–2137.

 PubMed Web of Science ®Google Scholar

Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, Mohamed N, et al. 2019. Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: virtual screening, synthesis, biological evaluation and molecular modelling. PLoS ONE. 14(1):e0210869. doi:10.1371/journal.pone.0210869.

 PubMed Web of Science ®Google Scholar

Qaddir I, Rasool N, Hussain W, Mahmood S. 2017. Computer-aided analysis of phytochemicals as potential dengue virus inhibitors based on molecular docking, ADMET and DFT studies. J Vector Borne Dis. 54:255–262.

 PubMed Web of Science ®Google Scholar

Paul A, Vibhuti A, Raj S. 2016. Molecular docking NS4B of DENV 1-4 with known bioactive phyto-chemicals. Bioinformation. 12(3):140–148.

 PubMed Web of Science ®Google Scholar

Qamar MTU, Maryam A, Muneer I, Xing F, Ashfaq UA, Khan FA, Anwar F, et al. 2019. Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus. Sci Rep. 9(1433):1–16.

 Google Scholar

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.