Antiviral Medicinal Plants of Veterinary Importance: A Literature Review^[#]

Abstract

Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families–Herpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Poxviridae, Nimaviridae, Coronaviridae, Reoviridae, and Rhabdoviridae–that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.

 

MissingLinkText

Key words

antiviral - plant - animal - herb - Herpesviridae - Orthomyxoviridae

Abbreviations

AMPV: avian metapneumovirus (Pneumoviridae)

AcNPV: Autographa californica nuclear polyhedrosis virus (Baculoviridae)

ARV: avian reovirus = avian orthoreovirus (Reoviridae)

AIV: avian influenza virus (Orthomyxoviridae)

BCV: bovine coronavirus (Coronaviridae)

BoHV-1: bovine herpesvirus type 1 (Herpesviridae)

BoHV-2: bovine herpesvirus type 2 (Herpesviridae)

BoHV-5: bovine herpesvirus type 5 (Herpesviridae)

BPXV: buffalopox virus (Poxviridae)

BRV: bovine rotavirus (Reoviridae)

BQCV: black queen cell virus in honeybee (Dicistroviridae)

BVDV: bovine viral diarrhea virus (Flaviviridae)

EAV: equine arteritis virus (Arteriviridae)

EDSV: egg drop syndrome virus (Flaviviridae)

EHSV: equine herpes simplex virus (Herpesviridae)

FWPV: fowlpox virus (Poxviridae)

GPV: goose parvovirus (Parvoviridae)

GTPV: goat poxvirus (Poxviridae)

IBDV: infectious bursal disease virus (Birnaviridae)

IBV: avian infectious bronchitis virus (Coronaviridae)

IHNV: infectious haematopoietic necrosis virus (Rhabdoviridae)

ILTV: infectious laryngotracheitis virus (Herpesviridae)

KHV: koi herpesvirus (Alloherpesviridae)

NDV: Newcastle disease virus (Paramyxoviridae)

OMV: oncorhynchus masou virus (Herpesviridae)

PPMV-1: paramyxovirus type 1 (Paramyxoviridae)

PPV: porcine parvovirus (Parvoviridae)

PRRSV: porcine respiratory and reproductive syndrome virus (Arteriviridae)

RABV: rabies virus (Rhabdoviridae)

RPV: Rinderpest virus (Paramyxoviridae)

SIV: swine influenza virus (Orthomyxoviridae)

SuHV-1: suide herpesvirus type 1 (Herpesviridae)

VHSV: viral haemorrhagic septicaemia virus (Rhabdoviridae)

WHV: woodchuck hepatitis virus (Hepadnaviridae)

WNV: West Nile Virus (Flaviviridae)

WSSV: white spot syndrome virus in marine shrimp (Nimaviridae)

YHV: yellow head virus in shrimp (Roniviridae)
 

Introduction

Viruses are unavoidable intracellular parasites that use the hostʼs cellular machinery to survive and multiply [1], often leading to serious diseases in both animals and humans. Antiviral drug resistance is an increasing concern in the immunocompromised patient population, where ongoing viral replication and prolonged drug exposure result in the emergence of resistant strains [2]. The ever-increasing need for antiviral drugs is even more pronounced presently owing to unsatisfying and limited treatment modalities. Hence, medicinal plants with their diversified secondary plant compounds have promising potential to provide a solution regarding this.

In the underdeveloped regions of the world, herbal medicines still play a crucial role in the treatment of sick animals because of the lack of educated veterinarians and financial resources, as well as the low availability of modern pharmaceuticals [3], [4]. Therefore, medicinal plants and products have been used since ancient times in ethnomedicine and ethnoveterinary medicine [3], often without knowledge of the pathogen or the mode of action of the remedies. Nevertheless, the search for plant substances effective against animal viruses that cause high mortality or significant economic losses has garnered interest in the last few decades.

Domesticated animals, particularly pigs, poultry, and horses, and more recently, dogs and cats, have been noted to experience influenza infections that have the potential to transmit across species to other animals, as well as humans. Swine influenza virus infections are frequently detected among humans with exposure to pigs and become transmissible between humans more often than avian influenza viruses [5]. The current research is focused on antiviral substances against viruses that transmit across species, such as the coronavirus causing severe acute respiratory syndrome (SARS) during the 2002 – 2003 pandemic or the recent coronavirus outbreak originating from China (SARS-CoV-2).

The second half of the 20th century discovered the antiviral activities of some vegetable tannins and flavonoids [6], [7], such as the polyphenols of Melissa officinalis L. (Lamiaceae) [8] and triterpenoids like dammaradienol and ursonic acid [9]. The antiviral activity of flavonoids was soon determined to be effective against adenoviruses, Rous sarcoma virus, Sindbis virus, pseudorabies virus [10], [11], severe acute respiratory syndrome coronavirus (SARS-CoV), respiratory syncytial virus, and influenza A virus H1N1 [12]. Epigallocatechin gallate, a compound of tea (Camellia sinensis (L.) Kuntze, Theaceae), has exhibited a broad range of activity against DNA and RNA viruses [13]. Several plant species, such as Vaccinium angustifolium Aiton (Ericaceae), Vitis vinifera L. (Vitaceae), and Cinnamomum species (Lauraceae), contain procyanidins that were shown to inhibit the replication of influenza A virus at various stages of the life cycle [14]. However, bioavailability and bioefficacy studies of polyphenols in humans revealed a wide variability of the data of different polyphenols after ingestion. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least absorption was found for proanthocyanidins, galloylated tea catechins, and anthocyanins [15]. But these data cannot be directly transferred to animals. Bioavailability and bioefficacy of polyphenolic compounds has to be studied in each animal species separately.

Prominent modes of action against viruses are inhibition of viral entry and its replication in the host cell via different mechanisms. Some of these plant compounds could inhibit cellular receptor kinases, thereby interfering with cellular signal transduction [1]. The challenges of drug treatment involve low efficiencies, cytotoxic effects, and development of viral resistance against them.

Over the last decade, the antiviral activity of several biological substances could be proven in vitro because of new testing methods. Even though several studies exist regarding the antiviral activities of plant extracts against human viruses, mainly HIV and herpesviruses [16], [17], [18], similar studies concerning animal viruses are scarce. Therefore, the objective of this review was to survey plant species with activities against viruses causing serious diseases, particularly those with high infection rates leading to a high mortality or large economic losses. The review primarily focused on the kind of extract, fraction, or isolated substance of a specific plant part and the design of the trial conducted.

 

MissingLinkText

Methods

The methods of this systematic review were based on the recommendations of the PRISMA statement [19], [20] and the AMSTAR measurement tool [21].

The literature research for this review was performed in 2 periods. The first period ranged from February to end of August 2014, and 1 person screened 4 books on ethnoveterinary medicine [22], [23], [24], [25] for antiviral plant species, as well as searched in databases, such as Scopus, Ovid, ISI Web of Science, and Google Scholar by using the search words “antiviral”, “plant”, “veterinary medicine”, and “virus” [26].

In the second period in 2019, 1 person used Ovid (Medline) and CAB Direct for a structured search. The keywords used for the search in January 2019 were “antiviral” AND “plant” or “herb” AND “animal”. In order to select the information about specific animal viruses in the following months, combinations of keywords consisting of the scientific abbreviation or the full name of an animal virus causing a serious animal disease (such as “NDV”, “BoHV”, etc.) AND “antiviral” AND “plant” were used. Notably, only English key words were applied. Moreover, a manual search was performed based on the bibliographic references of the articles found. The search was not limited by year of publication. Not all publications published in 2019 concerning the relevant virus species could be covered in this review, because the search of combination of keywords as described above was performed over several months. Search in December 2019 included a slightly longer period than in January 2019. The titles and abstracts of the obtained publications ([Fig. 1]) were screened manually and read by 1 person. Inclusion or exclusion was performed per the predefined inclusion and exclusion criteria, and duplicates generated in both searches in 2014 and 2019 were removed.

Fig. 1 Process of the literature search.

The publications were included based on the following criteria:

1. Only peer-reviewed publications with an abstract written in English were considered.

2. Publications had to describe assays testing plant species in vitro, in ovo, or in vivo for their antiviral effects against virus species causing serious infections in pigs, birds, ruminants, horses, shrimps, fish, or bees.

3. Publications that indicated the scientific name of the virus and its abbreviation.

4. Those that confirmed the identification of the used plant species.

5. Publications that described the method of extraction, fractionation, or isolation of compound(s) of the plant species.

6. Publications with proven antiviral activities of the plant species against viruses causing notifiable diseases [27], [28] or diseases with high infection rate leading to high mortality or large economic losses.

Publications without an abstract, presented only in conferences, and not in peer-reviewed journals, investigating a mixture of different plant species or extracts in a combined preparation or evaluating blends of several essential oils or mixtures of commercially available pure essential oil compounds were excluded. Furthermore, publications dealing with viruses that primarily caused infections of humans; publications studying the improvement of the immunity through immune stimulatory or immune boosting activities of plant extracts without explicit antiviral effects in infected animals; publications dealing with enhancement of immune responses to virus vaccine by supplementation of plant extract; studies testing the antiviral activity of a plant extract, fraction, or compound without success, as well as those testing viruses in a mouse or rat model, were excluded from the present review. Full text was retrieved of the publications that were eventually included.

In some publications, extracts, fractions, or compounds of numerous plant species were tested. Only those plant species that exhibited a proven antiviral activity against a specific animal virus species causing a serious disease are listed in [Table 1] and Table 1S, Supporting Information. Those plant species that were investigated but did not exhibit any antiviral activity were not mentioned in this review. In many publications, several extracts of different plant species were investigated against 1 or more virus species and in some of them even with different methods (in vitro, in ovo, or in vivo).

Table 1 Compilation of plant species exhibiting antiviral activity against more than 1 animal virus causing notifiable diseases (virus marked in bold) or diseases with high infection rate leading to high mortality or large economic losses; plant family; abbreviation of virus species; reference; plant part used for obtaining extracts, fractions or compound(s); power of activity; and design of the trial.

Plant species	Plant family	Virus species	Ref.	Extract/fraction/ compound(s)	Plant part	Activity	Design of trial
CC: cytotoxic concentration, dpi: day post infection, EC: effective concentration, EI: embryo index, EID: egg infective dose, HAI: hemagglutination inhibition, HPS: histopathological score, IC50: 50% inhibitory concentration, IP: inhibition percentage, IR: infectivity reduction, MNCC: maximal noncytotoxic concentration, MNTC: maximal nontoxic concentration, prot: protection, PRR: plaque reduction rate, n. a.: information not available, SI50: selectivity index (CC50/IC50), SR: survival rate, TI: therapeutic index (CC50/IC50), v. d.: virus dilution, VII: viral inhibition index
Acacia nilotica (L.) Delile	Leguminosae	BoHV-1	[40]	hot aqueous extract	leaf and pod	L: prot: 61.1% (0.156 mg/mL), 43.2% (0.078 mg/mL); P: prot: 22.1% (0.039 mg/mL), 14.4% (0.019 mg/mL)	in vitro
		GTPV	[83]	aqueous extract	leaf	EC50: 3.75 µg/mL, TI: 127.1	in vitro
Allium sativum L.	Amaryllidaceae	NDV	[43]	aqueous extract	bulb	EID50: no infection; garlic extract: 25 mg/mL; 50 mg/mL	in ovo
		IBV	[76]	aqueous extract	clove	EI: 1296 ± 269 (v. d. 10−2), 2604 ± 1251 (v. d. 10−3); garlic extract: 400 mg/mL	in ovo
		AIV H9N2	[84]	aqueous extracts	clove	HPS: 2.0; 15% dry extract of 10 g cloves in 100 mL	in ovo
Aloe hijazensis = Aloe castellorum J. R. I. Wood	Xanthorrhoeaceae	AIV H5N1, NDV, EDSV	[85]	ethanolic extracts	leaf, flower, root	CC50: > 500 – 800; IC50: ≤ 5 – 9; TI: 62.5 – 160	in ovo
Aristolochia bracteolate Lam.	Aristolochiaceae	NDV, FWPV	[57]	MeOH extract	leaf, fruit	HAI: L/F: 7/15% (100 µg/mL); 57.5/22.5% (200 µg/mL)	in ovo
Avicennia marina (Forssk.) Vierh.	Acanthaceae	NDV, FWPV	[57]	MeOH extract	leaf, stem	HAI: L/S: 7/7% (100 µg/mL); 22.5/22.5% (200 µg/mL)	in ovo
Azadirachta indica A. Juss.	Meliaceae	BoHV-1	[39]	aqueous extract, pectic arabinogalactan and derivative	leaf	IC50: 31.12 – 105.25 µg/mL; CC: > 1600 – 1440 µg/mL	in vitro
		FWPV	[86]	aqueous extract	leaf	n. a.	in vitro
		IBDV NDV	[87]	different extracts	leaf, fruit	CC50: > 200 – 900 µg/mL; IC50: ≤ 3 – 9 µg/mL; TI: > 66 – 120	in vitro and in ovo
Banisteriopsis variabilis B. Gates	Malphigiaceae	BoHV-1, ARV	[31]	crude aqueous extract	leaf	CC: 624 – 125 µg/mL; VII: 2.79/2.69; IP: 99/99%	in vitro
Bumelia sertorum Mart.	Sapotaceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 250 µg/mL; VII: ≥ 1.5	in vitro
Byrsonima intermedia A. Juss.	Malphigiaceae	BoHV-1, ARV	[31]	crude aqueous extract	leaf	CC: < 125 µg/mL; VII: 2.67/1.50; IP: 99/97%	in vitro
Camellia sinensis (L.) Kuntze	Theaceae	AIV H7N3	[88]	hot aqueous green tea extract	leaf	IC: 80 mg/mL	in ovo
		AIV H5N2	[89]	hot aqueous black tea extract	leaf	log10 reduction: ≥ 3.7	in vitro
		BRV	[75]	several theaflavins	leaf	EC50: 0.125 – 251.39 µg/mL	in vitro
		BCV	[75]	aqueous green tea extract	leaf	EC50: 34.7 µg/mL	in vitro
		ILTV	[90]	hot aqueous extract, epigallocatechin-3-gallate	leaf	MNCC: 90 µM; EC50: 4.22 µM	in vitro
Campomanesia xanthocarpa (Mart.) O. Berg	Myrtaceae	BoHV-1, ARV	[31]	crude aqueous extract	leaf	CC: 624 – 125 µg/mL; VII: 2.08/1.50; IP: 99/97%	in vitro
Caralluma retrospiciens (Ehrenb.) N. E.Br.	Apocynaceae	NDV, FWPV	[57]	MeOH extract	herb	HAI: 22.5% (100 and 200 µg/mL)	in ovo
Castanea spp.	Fagaceae	ARV, AMPV	[73]	Silvafeed (ENC, ENC400, CE) 77 – 91% hydrolysable tannins	wood	CC50: 243 – 272 µg/mL; IC50: 38 – 59 µg/mL	in vitro
Cissus quadrangularis L.	Vitaceae	NDV, FWPV	[57]	MeOH extract	herb	HAI: 22.5% (100 µg/mL); 7% (200 µg/mL)	in ovo
Coffea arabica L.	Rubiaceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 250 µg/mL; VII: ≥ 1.5	in vitro
Diospyros mespiliformis Hochst. ex A.DC.	Ebenaceae	NDV, FWPV	[57]	MeOH extract	bark, leaf	HAI: 100%, (100 and 200 µg/mL)	in ovo
Echinacea purpurea (L.) Moench	Asteraceae	AIV (H5N1, H7N7), SIV H1N1	[47]	Echinaforce, EtOH (65%)	herb, root	MIC100: 0.32 µg/mL for 102 PFU/mL; 7.5 µg/mL for 105 PFU/mL virus	in vitro
Emilia sonchifolia (L.) DC. ex DC.	Asteraceae	WSSV, YHV	[64]	acetone extract and fractions, 1 containing 2,4-di-tert-butylphenol	leaf	100 µg/mL	in vitro
Endopleura uchi (Huber) Cuatrec.	Humiriaceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 250 µg/mL; VII: ≥ 1.5	in vitro
Eugenia jambolana Lam. = Syzygium cumini (L.) Skeels	Myrtaceae	BPXV	[91]	aqueous extract	leaf	MNTC: 1999.73 µg/mL; EC50: 134 µg/mL; TI: 56.47	in vitro
		GTPV	[83]	aqueous extract	leaf	EC50: 46.5 µg/mL, TI: 162.7	in vitro
Excoecaria agallocha L.	Euphorbiaceae	IBDV, FWPV, RPV	[92]	latex	n. a.	n. a.	in vitro
Glycyrrhiza glabra L.	Leguminosae	NDV	[44]	aqueous extract	n. a.	0.6 mg/mL	in ovo
		PPMV-1	[34]	spray dried aqueous solution of extract	root	300 or 500 mg/kg BW, 7 dpi; viral RNA copy number in livers and kidneys 4-fold lower than in control group	in vivo
Guiera senegalensis J. F. Gmel.	Combretaceae	FWPV	[58], [59], [60]	aqueous decoctions, aqueous acetone extract	gall	in vitro: CC50: 90 µg/mL; EC50: 15.6 µg/mL; SI: 5.8; in ovo: MNTC: 250 µg/mL; 1.9 log reduction of virus titre at 25 µg/mL and 2.9 log at 250 µg/mL; in vivo: 100 mg/kg BW	in vitro, in ovo, in vivo
		EHSV	[93]	fractionated ethanolic (80%) extract	leaf	EC: 20 µg/mL, 75% inhibition	in vitro
Harrisonia abyssinica Oliv.	Rutaceae	NDV, FWPV	[57]	MeOH extract	leaf, fruit	HAI: L/F: 30%/15% (100 µg/mL); 7%/7% (200 µg/mL)	in ovo
Hypericum perforatum L.	Hypericaceae	PRRSV	[29], [94], [95]	extract, hypericin, pseudohypericin	n. a.	in vivo: extract: 200 mg/kg BW	in vitro and in vivo
		AIV H5N1	[96], [97]	liquid extract, hypericin	n. a.	n. a.	in vitro and in vivo
Isatis tinctoria L. = Isatis indigotica Fortune	Brassicaceae	PPV	[54]	n. a.	root	310 – 630 µg/mL	in vitro
		AIV (H6N2, H7N3, H9N2)	[98]	root-derived clemastanin B	root	IC50: 88 – 370 µg/mL	in vitro
		GPV	[56]	root derived polysaccharides	root	72 h p. i. 40 µg polysaccharides, 23 highest dilution of pos. allantoic fluid; average survival time 192 h with survival rate 6/6	in ovo
Lantana camara L.	Verbenaceae	AIV (A/H9N2, A/H5N1)	[14]	extract according to Chinese Pharmacopoeia	procyanidin	n. a.	in vitro
		WSSV	[63]	aqueous extract	n. a.	150 mg/kg BW	in vivo
Lavandula coronopifolia Poir.	Lamiaceae	NDV, FWPV	[57]	MeOH extract	herb	HAI: 100%, (100 and 200 µg/mL)	in ovo
Leandra purpurascens (DC.) Cogn.	Melastomataceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 125 µg/mL; VII: ≥ 1.5	in vitro
Lippia graveolens Kunth	Verbenaceae	BoHV-2	[42]	commercial essential oil	n. a.	CC50: 568 µg/mL; EC50: 58.4 µg/mL; SI50: 9.7	in vitro
				carvacrol	pure substance	CC50: 215 µg/mL; EC50: 663 µg/mL; SI50: 0.3	in vitro
		BVDV	[42]	commercial essential oil	n. a.	CC50: 568 µg/mL; EC50: 78 µg/mL; SI50: 7.2	in vitro
				carvacrol	pure substance	CC50: 215 µg/mL; EC50: 50.7 µg/mL; SI50: 4.2	in vitro
Maerua oblongifolia (Forssk.) A. Rich.	Capparaceae	NDV, FWPV	[57]	MeOH extract	leaf	HAI: 15% (100 µg/mL); 7% (200 µg/mL)	in ovo
Melissa officinalis L.	Lamiaceae	NDV	[8]	aqueous extract	leaf	n. a.	in vitro, in ovo
		AIV H9N2	[99]	essential oil	leaf	5 µg/mL reduced TCID50 to 1.9 (log 10); 500 µg/mL to 0.98 (log 10) in pre-infection stage	in vitro
		KHV	[100]	aqueous dry extract	leaf	extract in feed: 1.62%, SR: 45% (9/20)	in vivo
Momordica charantia L.	Cucurbitaceae	WSSV	[63]	methanol extract	n. a.	150 mg/kg BW	in vivo
		IHNV, OMV	[101]	n. a.	n. a.	PRR: IHNV: 68%; OMV: 47%	in vitro
Nigella sativa L.	Ranunculaceae	NDV, FWPV	[57]	methanolic extract	seed	HAI: 100%, (100 and 200 µg/mL)	in ovo
		ILTV	[90]	hot aqueous extract, thymoquinone	seed	MNCC: 80 µM; EC50: 35 µM	in vitro
Olea europaea L.	Oleaceae	VHSV	[102]	extract, oleuropein	leaf	VHSV: conc.: n. a.; IR: extract 10%; oleuropein 30%	in vitro
		ILTV	[103]	aqueous extract	leaf	CC50: 1250 µg/mL; IC50: 5.89 µg/mL	in vitro
Origanum vulgare L.	Lamiaceae	EAV	[104]	ethanolic extract, isolated compounds (phenolic acids, kaempferol, apigenin, quercetin)	leaf	NTC: 12.5 µg/mL; log10 TCID50/100 µL extract: 1.25; quercetin: 0.6, control: 6.08	in vitro
			[105]	aqueous (AE) and ethanolic extract (EE)	leaf	NTC: AE: 1600 µg/mL; EE: 600 µg/mL; log10 TCID50/100 µL: AE: 2.09; EE: 0.79, control: 5.42	in vitro
		SuHV-1	[38]	crude aqueous extract	leaf	CC: 62.5 µg/mL; VII: ≥ 1.5	in vitro
Phyllantus amarus Schumach & Thonn.	Phyllantaceae	WSSV	[63]	aqueous extract	n. a.	150 mg/kg BW	in vivo
			[65], [66]	acetone and petroleum ether extracts	leaf	dose: n. a., SR: 100% (9/9)	in vivo
			[101]	n. a.	n. a.	SR: 58%	in vivo
		IHNV, OMV	[101]	ethanolic extract	n. a.	CC50: 1.237 µg/mL; PRR: 100%	in vitro
		YHV	[101]	n. a.	n. a.	SR: 100%	in vivo
Prosopis chilensis (Molina) Stuntz	Leguminosae	NDV, FWPV	[57]	MeOH extract	leaf	HAI: 30% (100 µg/mL); 15% (200 µg/mL)	in ovo
Psidium cattleianum Afzel. ex Sabine	Myrtaceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 62.5 µg/mL; VII: ≥ 1.5	in vitro
Schinopsis spp.	Anacardiaceae	ARV, AMPV	[73]	Silvafeed NutriQ, 94% condensed tannins	wood	CC50: 254 µg/mL; IC50: 21 – 66 µg/mL	in vitro
Synadenium glaucescens Pax	Euphorbiaceae	IBDV, FWPV	[61]	ethanolic extract	root bark	200 µg/mL; SR: 100% (5/5); significantly higher mean embryo weight	in ovo
Uncaria tomentosa (Willd. ex Schult.) DC.	Rubiaceae	BoHV-1, SuHV-1	[38]	crude aqueous extract	leaf	CC: 500 µg/mL; VII: ≥ 1.5	in vitro
Zizyphus spina-christi (L.) Desf.	Rhamnaceae	NDV, FWPV	[57]	MeOH extract	leaf, bark	HAI: L/B: 22.5/100% (100 µg/mL); 0/100% (200 µg/mL)	in ovo

 

MissingLinkText

Results and Discussion

Overall, 72 publications related to 79 plant species with proven antiviral activities against animal virus species could be identified in 4 ethnoveterinary regions (24 plant species in Africa, 11 in Asia, 13 in Latin America, and 31 in Western Countries, including Europe, USA, and Canada) in the first part of the search [26] ([Fig. 1]).

From OVID (n = 5097) and CAB Direct (n = 3387) databases, 8484 publications were retrieved after the literature search in 2019 (second part of the search) by using the following combination of key words in “all fields”: “antiviral” AND “plant” AND “animal”. Removal of duplicates yielded 8324 publications. Restricting the search of the same terms to only the abstracts yielded titles of 497 publications, which were then manually screened, and 262 abstracts were selected ([Fig. 1]). After inclusion or exclusion per the predefined inclusion and exclusion criteria and removal of duplicates generated in both searches, 25 publications of the search in 2014 and 73 of the search of 2019 were included in this review.

Even though all databases used for the searches delivered several useful results, CAB Direct, including the databases CAB Abstracts and Global Health, which specializes in applied life sciences, provided the best results by using the most specific indexing terms in its databases.

In summary, 130 plant species with antiviral activity on 37 different animal virus species were compiled. This review noted several plant species that were active against virus species causing serious diseases in birds. The antiviral medicinal plant species exhibiting activities against serious veterinary viral pathogens are presented in Table 1S, Supporting Information. The literature review revealed 46 plant species that were active against pathogenic virus species of the virus family Herpesviridae, 31 plant species with antiviral activity against Paramyxoviridae, 30 against Orthomyxoviridae, 19 against Poxviridae, and 12 against Nimaviridae. Furthermore, this review included 9 plant species with activity against Reoviridae, 7 against Flaviviridae, 5 against Coronaviridae, 5 against Baculoviridae, 4 against Rhabdoviridae, and 1 to 3 plant species against viruses of 8 other virus families. Notably, some members of these virus families cause diseases with significant economic losses. However, the research interest varies among the different ethnoveterinary groups concerning the animals, plants, and viruses occurring in various areas and climates. For example, several African medicinal plants were tested for their effects against NDV (Paramyxoviridae), whereas numerous Asian and Latin American medicinal plants were tested against bovine herpes viruses (Herpesviridae).

Nevertheless, the present review only included plant species exhibiting an antiviral effect against virus species causing notifiable diseases per the World Organisation of Animal Health (OIE) [27] and the Austrian legislation [28]. A list of these diseases and the virus species causing them is provided in [Table 2]. Virus species causing these notifiable diseases are marked in bold in [Table 1] and Table 1S, Supporting Information. [Table 1] provides a compilation of the plant species that are active against more than 1 specific virus species, as well as informs regarding the plant part used in the preparation of the specific extract, fraction, or compound(s), the power of the antiviral activity, and the design of the trial (in vitro, in vivo, or in ovo). Direct comparison of the strength of the antiviral activity of different plant extracts is often difficult, because various testing methods were used. Therefore, if available, the 50% inhibitory concentration (IC₅₀) and the maximal nontoxic concentration (MNTC) of the plant extract found in in vitro and in ovo tests as well as the administered doses and the survival rate (SR) or the 50% effective concentration (EC₅₀) in in vivo trials were listed in [Table 1]. In some cases, antiviral activity was determined only at 2 nontoxic concentrations of the plant extract. Table 1S, Supporting Information, provides similar information regarding all plant species that were noted to be active against the virus species, based on the inclusion and exclusion criteria. A closer look into the design of the studies shows that 94 plant species were investigated in vitro, 37 in ovo on embryonated eggs, and 24 in vivo. A significant part of the in vivo studies was performed on poultry, shrimps, and crayfish. Only 1 study dealt with experimental infections of PRRSV on piglets [29] and 1 with hepatitis viruses on woodchuck [30]. The aqueous extract of Phyllanthus niruri L. (Phyllantaceae) was effective when administered i. p. in reducing and eliminating both the surface antigen titer and DNA polymerase activity in serum after experimental infections with WHV in woodchuck [30]. Notably, in vivo studies on mouse and rat models were excluded from the present review. The strategy to include in this review only the plant species found active against a specific virus in a cited study might produce a certain positive bias. It possibly happened only in a very few cases that a plant extract was tested against the same virus species with the same method and found active in 1 study and inactive in another study. However, even in those cases, it seems worth listing the plant species and the antiviral activity found against a specific animal virus in Table 1S, Supporting Information, and [Table 1], in order to encourage the scientific society to confirm or deny these activities in further studies.

Table 2 List showing notifiable diseases per the World Organisation of Animal Health (OIE) [27] and the legislation in Austria [28], virus species and their abbreviations, as well as virus family causing the particular disease in a specific host and number of plant species found active against the named virus.

Disease	Virus species	Abbreviation of virus	Family of virus	Host	Plant species
avian influenza	avian influenza virus	AIV	Orthomyxoviridae	poultry	26
infectious bovine rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV), and infectious balanoposthitis (IBP)	bovine herpesvirus type 1	BoHV-1	Herpesviridae	cattle	20
rotaviral diarrhea	bovine rotavirus	BRV	Reoviridae	cattle	1
bovine viral diarrhea	bovine viral diarrhea virus	BVDV	Flaviviridae	cattle	5
goatpox	goat poxvirus	GTPV	Poxviridae	goat	2
infectious hematopoietic necrosis infection	infectious hematopoietic necrosis virus	IHNV	Rhabdoviridae	fish	2
koi herpesvirus disease	koi herpesvirus	KHV	Alloherpesviridae	koi	2
Newcastle disease	Newcastle disease virus	NDV	Paramyxoviridae	poultry	30
rabies	rabies virus	RABV	Rhabdoviridae	multiple species	1
Rinderpest infection	Rinderpest virus	RPV	Paramyxoviridae	multiple species	1
pseudorabies	suide herpesvirus type 1	SuHV-1	Herpesviridae	pig	10
viral hemorrhagic septicemia infection	viral hemorrhagic septicemia virus	VHSV	Rhabdoviridae	fish	1
West Nile fever	West Nile virus	WNV	Flaviviridae	multiple species	1
white spot syndrome virus infection	white spot syndrome virus	WSSV	Nimaviridae	Crustacea	12
yellow head virus genotype 1 infection	yellow head virus genotype 1	YHV	Roniviridae	Crustacea	2

In the present review, it is not possible to describe the antiviral assays performed for each plant species. So that the reader gets an idea about the assays performed, usual work flows for in vitro, in ovo, and in vivo studies are described. Cytotoxicity assays were performed in vitro by exposure of cell strains (e.g., Madin-Darby bovine kidney [MDBK] or Vero cells) to the plant extracts in different concentrations following incubation in microtiter plates. Cell alterations were monitored microscopically or with specific dyes entering only dead cells to determine the MNTC compared to an untreated control. Then cells were incubated for a defined period of time with the plant extracts in dilutions corresponding to the MNTC and inoculated with dilutions of viruses corresponding to tissue culture infective dose (TCID₅₀). Controls consisted of untreated infected (virus titer), treated noninfected (extract control), and untreated noninfected (cell control) cells. Antiviral activities could be calculated as the difference of virus titer between treated infected and untreated infected control cultures [31].

During in ovo tests, different concentrations of the plant extracts were injected into allantoic cavity of 7-day-old embryonated chicken eggs, in order to find the MNTC. If the extracts were not toxic for the eggs, the chickens would be born alive and healthy after 2 wks of incubation. For the test of antiviral activity of the extracts, a virus strain (e.g., NDV) was inoculated to infection-free 9-day-old embryonated chicken eggs. After 4 days, the allantoic fluid was harvested, and hemagglutination (HA) test was applied to confirm the virus. Next, the plant extracts were mixed with different concentrations of the virus, and the mixture was inoculated after incubation to allantoic cavity of viable 7- to 10-day-old embryonated eggs. Uninoculated eggs and eggs with virus suspension without plant extract served as controls. The allantoic fluid was harvested 5 days after inoculation and analyzed for virus titer by a standard HA test. Antiviral activity of the plant extracts was measured by the reduction assay of viral titer and explained by inhibition percentage [32], [33].

As an example, for in vivo studies, the evaluation of the antiviral effectiveness of various doses of Aloe vera (L.) Burm.f. (Xanthorrhoeaceae) and Glycyrrhiza glabra L. (Leguminosae) extracts on the course of experimental PPMV-1 infection in pigeons is described [34]. The experiment was performed on pigeons divided into 5 groups, including 1 control group and 4 experimental groups, which were orally administered aloe vera or licorice extracts at 300 or 500 mg/kg BW for 7 days after experimental inoculation with PPMV-1. On day 4, 7, and 14 after inoculation, cloacal swabs and samples of organs were collected from 4 birds in each group. The samples were analyzed to determine the copy number of PPMV-1 RNA by TaqMan qPCR. The results indicated that both extracts inhibited PPMV-1 replication by decreasing viral RNA copy numbers in the examined organs (brain, kidney, and liver) compared to the control group [34].

The following sections present the information regarding virus families and their crucial members against which plant species were noted to exert antiviral activity, as evidenced in the literature.

Herpesviridae

Table 1S, Supporting Information, lists 20 plant species exhibiting antiviral effects against BoHV-1, 1 against BoHV-2, 2 against BoHV-5, 8 against EHSV, and 10 against SuHV-1. Moreover, Table 1S, Supporting Information, presents 3 plant species that exerted antiviral activity against ILTV and 2 plant species against the fish herpes virus, OMV.

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases of animals, as well as humans [35]. Overall, more than 130 herpesviruses are known [36], some of them noted in mammals, birds, fish, reptiles, amphibians, and molluscs [37].

One representative of this family is BoHV-1, subfamily Alphaherpesvirinae, known to cause several diseases in cattle worldwide, including rhinotracheitis, vaginitis, balanoposthitis, abortion, conjunctivitis, and enteritis. Although these symptoms are primarily nonlife-threatening, it is an economically critical disease because the infection causes a drop in production and affects trade restrictions. Like other herpesviruses, BoHV-1 causes a lifelong latent infection and sporadic shedding of the virus. Some European countries have successfully eradicated the disease by applying a strict culling policy.

Antiviral activities against BoHV-1 could be observed in several Brazilian medicinal plants, such as Banisteriopsis variabilis B. Gates (Malpigiaceae), Byrsonima intermedia A. Juss. (Malpigiaceae), Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae), Cissus erosa Rich. (Vitaceae), Erythroxylum deciduum A. St.-Hil. (Erythroxylaceae), Lacistema hasslerianum Chodat (Lacistemataceae), Ocotea pulchella (Nees & Mart.) Mez (Lauraceae), and Xylopia aromatica (Lam.) Mart. (Annonaceae) [31]. In addition, Bumelia sertorum Mart. (Sapotaceae), Coffea arabica L. (Rubiaceae), Endopleura uchi (Huber) Cuatrec. (Humiriaceae), Leandra purpurascens (DC.) Cogn. (Melastomataceae), Psidium cattleianum Afzel. ex Sabine (Myrtaceae), and Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) exhibited antiviral activity on BoHV-1 as well as SuHV-1 [38].

The activity of the leaf extract of Azadirachta indica A. Juss. (Meliaceae) against BoHV-1 is attributed to the polysaccharide arabinogalactan [39]. Hot aqueous extracts of Acacia nilotica (L.) Delile leaves exhibited a 3 times stronger antiviral effect against BoHV-1 than the pods [40].

BoHV-5, the bovine encephalitis herpesvirus, causes meningoencephalitis and respiratory disease in cattle and sheep. Hexane and ethyl acetate extracts of Plocamium brasiliense (Greville) M. Howe & W. R. Taylor (Plocamiaceae), a marine alga, inhibited virus attachment in MDBK cells [41].

Antiviral activity of the Lippia graveolens Kunth, Mexican oregano (Verbenaceae) essential oil and its main compound carvacrol was observed to be active against BoHV-2 [42]. The essential oil of L. graveolens provides the advantage to be effective against both RNA and DNA viruses. Besides herpesviruses, BVDV (Flaviviridae), a RNA virus, was also inhibited in the same study [42].

 

MissingLinkText

Paramyxoviridae

Citations of 30 plant species with activity against NDV were noted in the literature (Table 1S, Supporting Information). Recent investigations were performed on extracts of the brown leaves of Allium cepa L. (Amaryllidaceae) and the bulbs of Allium sativum L. (Amaryllidaceae) [43], ethanol/water extract of flowers of Achillea millefolium L. (Asteraceae) [32], and aqueous extract of G. glabra L. (Leguminosae) powder, all of which inhibited NDV in embryonated eggs [44].

As listed by the World Organisation for Animal Health (OIE), Newcastle disease is a disease of major significance in poultry and other birds. It is caused by specified viruses of the avian paramyxovirus type 1 of the family Paramyxoviridae [45]. The disease is characterized by respiratory or neural signs, partial or complete cessation of egg production or misshapen eggs, greenish watery diarrhea, and edema of the tissues around the eyes and the neck.

Fucoidan is a sulfated polysaccharide present in the cell wall matrix of the brown algae Cladosiphon okamuranus Tokida (Chordariaceae). It exhibited antiviral activity against NDV in the Vero cell line with low toxicity, and this inhibition was observed particularly in the early stages of infection [46].

 

MissingLinkText

Orthomyxoviridae

Well-known representatives of the family Orthomyxoviridae are the 4 genera of influenza viruses A – D. These viruses cause influenza in vertebrates, including birds, humans, and other mammals.

The literature revealed 30 plant species that exhibited activity against several types of influenza viruses (Table 1S, Supporting Information), mostly the ones causing avian influenza and swine flu.

Highly pathogenic avian influenza virus of the H5- and H7-types, as well as swine origin influenza (H1N1), were all inactivated in cell culture assays by the commercially available preparation of Echinacea purpurea (Echinaforce = EF) at different concentrations. Detailed studies with the H5N1 strain indicated that direct contact between EF and virus was required, before infection, to obtain maximum inhibition of virus replication. Hemagglutination assays revealed that the extract inhibited the receptor binding activity of the virus, suggesting that the extract interferes with the viral entry into cells. Upon sequential passage studies, no EF-resistant variants emerged during treatment in the cell culture with the H5N1 virus, in contrast to Tamiflu, which produced resistant viruses upon passaging. Furthermore, the Tamiflu-resistant virus was just as susceptible to EF as the wild type virus [47].

The review of Arora et al. [48] presented a list of medicinal plants used in Ayurveda and traditional Chinese medicine with antiviral effects against influenza, which could be useful in the management of H1N1 flu, the pandemic arising from swine flu.

Glycyrrhizin, a triterpene saponine of licorice root (G. glabra L.), was comprehensively investigated for its antiviral properties. It has been noted to interfere with replication or cytopathogenic effect induction in several viruses, including respiratory viruses and influenza viruses [49]. Michaelis et al. [50] studied the effect of glycyrrhizin on highly pathogenic H5N1 influenza A viruses in lung epithelial cells, which induce avian influenza but are considered potential influenza pandemic progenitors [51], [52]. Glycyrrhizin concentrations from 25 to 50 µg/mL substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL 10, IL-6, CCL2, and CCL5. However, for interference of H5N1 replication and H5N1-induced apoptosis, concentrations of 100 µg/mL or higher were necessary. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species, thereby reducing the activation of NFκB, JNK, and p38 redox-sensitive signaling events that are known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease [50].

Pterocarpans and flavanones isolated from Sophora flavescens Aiton (Leguminosae) were noted to inhibit neuraminidase, an enzyme crucial in the proliferation of the influenza virus [53].

 

MissingLinkText

Parvoviridae

Two plant species with antiviral activity against PPV were included in this review. PPV causes reproductive failure of swine characterized by embryonic and fetal infection and death, often without any outward maternal clinical signs. The virus is ubiquitous among swines worldwide and is enzootic in most herds that have been tested. Diagnostic surveys have indicated that PPV is the major infectious cause of embryonic and fetal death. The essential oil as well as aqueous extracts of Mentha spicata L. (Lamiaceae) [54] and Isatis tinctoria L. (Brassicaceae) [55] exhibited activity against PPV in vitro. Moreover, I. tictonia L. was active against GPV [56].

 

MissingLinkText

Poxviridae

Humans, vertebrates, and arthropods serve as natural hosts of Poxviridae. The virion is exceptionally large and carries its genome in a single, linear, double-stranded segment of DNA.

The literature reported antiviral activity of 16 plant species primarily against FWPV, 2 plant species against GTPV, and 1 plant species against BPXV (Table 1S, Supporting Information). Notably, methanolic extracts of different Sudanese medicinal plants were observed to exhibit antiviral activity against FWPV [57] as well as aqueous decoctions and acetone extracts of galls of Guiera senegalensis J. F. Gmel. (Combretaceae) in vitro, in ovo, and in vivo [58], [59], [60]. Treatments with an ethanolic extract of the root bark from Synadenium glaucescens Pax (Euphorbiaceae) demonstrated significantly higher mean embryo weight in an in ovo assay against FWPV compared with other extracts of the same plant [61].

 

MissingLinkText

Nimaviridae

WSSV of the family Nimaviridae is responsible for causing white spot syndrome in a wide range of crustacean hosts [62]. White spot syndrome is a viral infection of penaeid shrimp and causes severe economic losses to aquaculture. The disease is highly contagious and lethal, killing shrimps quickly [63]. Until date, there are no commercially available drugs to control the virus. This serious problem has been the focus of several recent investigations on medicinal plants with antiviral activity against WSSV, leading to 51 publications in CAB database. This review lists 12 plant species with activity against WSSV in Table 1S, Supporting Information, that were investigated in a study of 2007 [63] and described in 9 publications from 2014 to 2019 [64], [65], [66], [67], [68], [69], [70], [71], [72].

 

MissingLinkText

Reoviridae

Infection with avian orthoreovirus, also known as ARV, causes mainly arthritis and tenosynovitis in poultry. Aqueous extracts of 8 plant species [31], [73], [74] exhibited antiviral activity against ARV in vitro. BRV are the most common cause of neonatal diarrhea in calves. Clinical disease in calves older than 1 mo is rare. However, periodic asymptomatic re-infection and shedding occurs in older cows and calves. Theaflavins of C. sinensis (L.) Kuntze (Theaceae) were noted to be active against this virus [75].

 

MissingLinkText

Coronaviridae

Avian IBV is a coronavirus that infects chickens, causing infectious bronchitis. It is a highly infectious avian pathogen that affects the respiratory tract, gut, kidneys, and reproductive system of chickens. The aqueous extract of A. sativum L. (Amaryllidaceae) [76], the ethanolic (80%) extract of Sambucus nigra L. (Adoxaceae) [77], polysaccharides of Astragalus species [78], and the essential oil of Rosmarinus officinalis L. (Lamiaceae) [79] were determined to be active against IBV in vitro. Furthermore, theaflavins of C. sinensis (L.) Kuntze (Theaceae) exhibited activity against BCV [75].

 

MissingLinkText

Other viruses

The antiviral activity of plant extracts against viruses of insects was not the primary focus of this review. Therefore, only a few examples were presented in this review highlighting the possibilities to fight against viruses causing diseases in bees. Five plant species were noted to be active against AcNPV (Baculoviridae), namely Aconitum nasutum Fisch. ex Rchb. (Ranunculaceae), Hypericum androsaemum L. (Hypericaceae), Laurus nobilis L. (Lauraceae), Rhododendron caucasicum Pall. (Ericaceae), and Urtica dioica L. (Urticaceae) [80]. Furthermore, the antiviral potential of L. nobilis leaf ethanolic extract on forager honeybees naturally infected with BQCV (Dicistroviridae) [81] should not go unmentioned.

Antivirals display a variety of mechanisms of action, and while some block a specific enzyme or a particular stage in the viral replication cycle, others like zanamivir and oseltamivir have the ability to inhibit prokaryotic neuraminidase. More recent research has revealed antiviral activity of the following plant species during in vitro enzyme assay: Geranium sanguineum L. (Geraniaceae), Eucalyptus globulus Labill. (Myrtaceae), Ginkgo biloba L. (Ginkgoaceae), Echinacea angustifolia DC. (Asteraceae), and Zingiber officinale Roscoe (Zingiberaceae) [82]. Nevertheless, it is imperative to persevere with exploring and developing new antiviral compounds because viruses are continually evolving into new antiviral-resistant strains by virtue of their high mutation rate [1].

This review demonstrates that there exists an overwhelming number of plant species with the potential to fight against various highly pathogenic animal viruses, and these plant species need to be analyzed for their potential prophylactic and therapeutic applications. Notably, some plant species are promising candidates for developing new antiviral remedies that are required urgently.

 

MissingLinkText

 

MissingLinkText

Contributors’ Statement

Data collection: T. Marschik, K. Zitterl-Eglseer; design of the study: K. Zitterl-Eglseer, T. Marschik; analysis and interpretation of the data: T. Marschik, K. Zitterl-Eglseer; drafting the manuscript: T. Marschik, K. Zitterl-Eglseer; critical revision of the manuscript: K. Zitterl-Eglseer.

 

MissingLinkText

 

MissingLinkText

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgements

The authors would like to thank Enago (www.enago.com) for the English language review.

^# Dedicated to Prof. Wolfgang Kubelka on the occasion of his 85th birthday.

• References

• 1 Villa TG, Feijoo-Siota L, Rama JLR, Ageitos JM. Antivirals against animal viruses. Biochem Pharmacol 2017; 133: 97-116
• 2 Strasfeld L, Chou S. Antiviral drug resistance: mechanisms and clinical implications. Infect Dis North Am 2010; 24: 413-437
• 3 Wanzala W, Zessin KH, Kyule NM, Baumann MPO, Mathias E, Hassanali A. Ethnoveterinary medicine: a critical review of its evolution, perception, understanding and the way forward. Livest Res Rural Dev 2005; 17: #119
• 4 Edwards J. Global perspectives of veterinary education: reflections from the 27th World Veterinary Congress. J Vet Med Educ 2004; 31: 9-12
• 5 Borkenhagen LK, Salman MD, Ma MJ, Gray GC. Animal influenza virus infections in humans: a commentary. Int J Infect Dis 2019; 88: 113-119
• 6 Cutting WC, Dreisbach RH, Neff BJ. Antiviral chemotherapy; flavones and related compounds. Stanford Med Bull 1949; 7: 137
• 7 Fischer G, Gardell S, Jorpes E. On the chemical nature of acerin and the virucidal and antiviral effects of some vegetable tannins. Experientia 1954; 10: 329-330
• 8 Kucera LS, Herrmann EC. Antiviral substances in plants of the Mint family (Labiatae). I. Tannin of Melissa officinalis. Proc Soc Exp Biol Med 1967; 124: 865-869
• 9 Poehland BL, Carté BK, Francis TA, Hyland LJ, Allaudeen HS, Troupe N. In vitro antiviral activity of dammar resin triterpenoids. J Nat Prod 1987; 50: 706-713
• 10 Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 1995; 33: 1061-1080
• 11 Chiang LC, Chiang W, Liu MC, Lin CC. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother 2003; 52: 194-198
• 12 Wei F, Ma SC, Ma LY, But PPH, Lin RC, Khan IA. Antiviral flavonoids from the seeds of Aesculus chinensis. J Nat Prod 2004; 67: 650-653
• 13 Colpitts CC, Schang LM. A small molecule inhibits virion attachment to heparan sulphate- or sialic acid-containing glycans. J Virol 2014; 88: 7806-7817
• 14 Dai J, Wang G, Li W, Zhang L, Yang J, Zhao X, Chen X, Xu Y, Li K. High-throughput screening for anti-influenza A virus drugs and study of the mechanism of procyanidin on influenza A virus-induced autophagy. J Biomol Screen 2012; 17: 605-617
• 15 Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005; 81 (suppl) 230S-242S
• 16 Jassim SAA, Naji MA. Novel antiviral agents: a medicinal plant perspective. J Appl Microbiol 2003; 95: 412-427
• 17 Mukhtar M, Arshad M, Ahmad M, Pomerantz RJ, Wigdahl B, Parveen Z. Antiviral potentials of medicinal plants. Virus Res 2008; 131: 111-120
• 18 Akram M, Tahir IM, Shah SMA, Mahmood Z, Altaf A, Ahmad K, Munir N, Daniyal M, Nasir S, Mehboob H. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: a systematic review. Phytother Res 2018; 32: 811-822
• 19 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62: e1-e34
• 20 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097
• 21 Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, Porter AC, Tugwell P, Moher D, Bouter LM. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007; 7: 10
• 22 Wynn SG, Fougére BJ. eds. Veterinary herbal Medicine. St. Louis, MO: Mosby Elsevier; 2007
• 23 Watson RR, Preedy VR. eds. Botanical Medicine in clinical Practice. Wallingford: CABI; 2008
• 24 Mathias E, McCorkle M. Ethnoveterinary Research and Development. London: Intermediate Technology Publications; 1996
• 25 Katerere DR, Luseba D. Ethnoveterinary botanical medicine, herbal medicines for animal health. Boca Raton: CRC Press; 2010
• 26 Marschik T. Literaturstudie über die antivirale Wirkung von Heilpflanzen und ihrer Anwendung in der Veterinärmedizin [Diploma thesis]. Vienna: University of Veterinary Medicine; 2014
• 27 World Organisation for Animal Health (OIE). Aquatic and terrestrial animal health codes. Paris: 2020. Available at (Accessed April 1, 2020): https://www.oie.int/en/animal-health-in-the-world/oie-listed-diseases-2020
• 28 Tierseuchengesetz (TSG), Gesetz betreffend die Abwehr und Tilgung von Tierseuchen konsolidierte Fassung vom 2.4.2020, Austria, § 16 anzeigepflichtige Seuchen; 1909. Available at (Accessed April 2, 2020): https://www.jusline.at/gesetz/tsg/paragraf/16
• 29 Pu X, Liang J, Shang R, Wang X, Wang Z, Hua L, Liu Y. Influence of Hypericum perforatum extract on piglet infected with porcine respiratory and reproductive syndrome virus. Agric Sci China 2009; 8: 730-739
• 30 Venkateswaran PS, Millman I, Blumberg BS. Effects of an extract from Phyllanthus niruri on hepatitis B and Woodchuck hepatitis viruses: in vitro and in vivo studies. Proc Natl Acad Sci U S A 1987; 84: 274-278
• 31 Simoni IC, Manha APS, Sciessere L, Hoe VMH, Takinami VH, Fernandes MJB. Evaluation of the antiviral activity of Brazilian Cerrado plants against animal viruses. Virus Rev Res 2007; 12: 110
• 32 Rezatofighi SE, Seydabadi A, Seyyed Nejad SMS. Evaluating the efficacy of achillea millefolium and thymus vulgaris extracts against Newcastle disease virus in ovo . Jundishapur J Microbiol 2014; 7: e9016
• 33 Bakari GG, Max RA, Mdegela RH, Phiri EC, Mtambo MM. Antiviral activity of crude extracts from Commiphora swynnertonii against Newcastle disease virus in ovo . Trop Anim Health Prod 2012; 44: 1389-1393
• 34 Dziewulska D, Stenzel T, Smialek M, Tykalowski B, Koncicki A. An evaluation of the impact of aloe vera and licorice extracts on the course of experimental pigeon paramyxovirus type 1 infection in pigeons. Poult Sci 2018; 97: 470-476
• 35 Mettenleiter TC, Sobrino F. Animal Viruses: Molecular Biology. Poole, UK: Caister Academic Press; 2008
• 36 Brown JC, Newcomb WW. Herpesvirus capsid assembly: insights from structural analysis. Curr Opin Virol 2011; 1: 142-149
• 37 Carter J, Saunders V. Virology, Principles and Application. Hoboken, New Jersey: John Wiley & Sons; 2007
• 38 Fernandes MJB, Barros AV, Melo MS, Simoni I. Screening of Brazilian plants for antiviral activity against animal herpesviruses. J Med Plants Res 2012; 12: 2261-2265
• 39 Saha S, Gahardi LCF, Yamamoto AK, Linhares REC. Water-extracted polysaccharides from Azadirachta indica: structural features, chemical modification and anti-bovine herpes type 1 (BoHV-1) activity. Int J Biol Macromolec 2010; 47: 640-645
• 40 Gupta D, Goel A, Bhatia AT. Studies on antiviral property of Acacia nilotica . J Environ Res Develop 2010; 5: 141-152
• 41 Pinto AMV, Leite JPG, Ramos CJB, da Fonseca RR, Teixeira VL, Paixão ICNP. Anti-herpesvirus bovine type 5 activities of extracts obtained from Plocamium brasiliense . J Appl Phycol 2014; 26: 2021-2027
• 42 Pilau MR, Alves SH, Weiblen R, Arenhart S, Cueto AP, Lovato LT. Antiviral activity of the Lippia graveolens (Mexican oregano) essential oil and its main compound carvacrol against human and animal viruses. Braz J Microbiol 2011; 42: 1616-1624
• 43 Harazem R, Rahman S, Kenawy A. Evaluation of antiviral activity of Allium cepa and Allium sativum extracts against Newcastle disease virus. Alex J Vet Sci 2019; 61: 108-118
• 44 Omer MO, Almalki WH, Shahid I, Khuram S, Altaf I, Imran S. Comparative study to evaluate the anti-viral efficacy of Glycyrrhiza glabra extract and ribavirin against the Newcastle disease virus. Pharmacogn Res 2014; 6: 6-11
• 45 Diel DG, Da Silva LH, Liu H, Wang Z, Miller PJ, Afonso CL. Genetic diversity of avian paramyxovirus type 1: proposal for a unified nomenclature and classification system of Newcastle disease virus genotypes. Infect Genet Evol 2012; 12: 1770-1779
• 46 Elizondo-Gonzalez R, Cruz-Suarez LE, Ricque-Marie D, Mendoza-Gamboa E, Rodriguez-Padilla C, Trejo-Avila LM. In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle disease virus. Virol J 2012; 9: 307
• 47 Pleschka S, Stein M, Schoop R, Hudson JB. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV). Virol J 2009; 6: 197-205
• 48 Arora R, Chawla R, Marwah R, Arora P, Sharma RK, Kaushik V, Goel R, Kaur A, Silambarasan M, Tripathi RP, Bhardwaj JR. Potential of complementary and alternative medicine in preventive management of novel H1N1 flu (swine flu) pandemic: thwarting potential disasters in the bud. J Evid Based Complement Altern Med 2011; 2011: 586506
• 49 Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J. Antiviral effects of Glycyrrhiza species. Phytother Res 2008; 22: 141-148
• 50 Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, Cinatl J. Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS One 2011; 6: e19705
• 51 Cinatl Jr J, Michaelis M, Doerr HW. The threat of avian influenza A (H5N1). Part III: Antiviral therapy. Med Microbiol Immunol 2007; 196: 203-212
• 52 Michaelis M, Doerr HW, Cinatl J. Of chickens and men: avian influenza in humans. Curr Mol Med 2009; 9: 131-151
• 53 Ryu YB, Curtis-Long MJ, Kim JH, Jeong SH, Yang MS, Lee KW, Lee WS, Park KH. Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition. Bioorg Med Chem Lett 2008; 18: 6046-6049
• 54 Zhong H, Zhao BY, Fan GY, Liu JW, Chen JJ. Study on inhibitive effect of Radix Astragali and Radix Isatidis in vitro on porcine parvovirus. J Northwest A & F University (Natural Science Edition) 2008; 36: 48-52
• 55 Han WL, Cui BA, Zhang HY, Wang XB, Xu DH, Chen RL. Antiviral activity of Mentha spicata Linn. Extracts against porcine parvovirus in vitro . Jiangsu J Agric Sci 2011; 27: 556-560
• 56 Xu XQ, Li Q, Gao PG, Fan YY, Wang ZG. Antivirus effects of IRPS against goose parvovirus in goose embryo. Chin J Vet Sci 2008; 28: 1340-1343
• 57 Ietidal ETM, El Bushra ESEN, Mahasin ENA. The antibacterial, antiviral activities and phytochemical screening of some Sudanese medical plants. Eurasian J Biosci 2010; 4: 8-16
• 58 Lamien CE, Meda A, Couacy-Hymann E, Ouedraogo AG, Nacoulma OG. The phytochemical composition and in vitro antiviral activity of decoctions from galls of Guiera senegalensis J.F. Gmel. (Combretaceae) and their relative non-toxicity for chickens. Onderstepoort J Vet Res 2005; 72: 111-118
• 59 Lamien CE, Meda A, Mans J, Romito M, Nacoulma OG, Viljoen GJ. Inhibition of fowlpox virus by an aqueous acetone extract from galls of Guiera senegalensis J.F. Gmel (Combretaceae). J Ethnopharmacol 2005; 96: 249-253
• 60 Lamien CE, Mans J, Meda A, Couacy-Hymann E, Romito M, Ouedraogo AG, Nacoulma OG, Viljoen GJ. In ovo inhibition of fowlpoxvirus replication by a gall extract from Guiera senegalensis . Avian Pathol 2005; 34: 127-132
• 61 Mabiki FP, Mdegela RH, Mosha RD, Magadula JJ. Antiviral activity of crude extracts of Synadenium glaucescens (pax) against infectious bursal disease and fowlpox virus. J Med Plants Res 2013; 7: 871-876
• 62 Wang HC, Hirono I, Maningas MBB, Somboonwiwat K, Stentiford G. Ictv Report Consortium. ICTV virus taxonomy profile: Nimaviridae. J Gen Virol 2019; 100: 1053-1054
• 63 Balasubramanian G, Sarathi M, Kumar SR, Hameed ASS. Screening the antiviral activity of Indian medicinal plants against white spot syndrome virus in shrimp. Aquaculture 2007; 263: 15-19
• 64 Maikaeo L, Chotigeat W, Mahabusarakam W. Emilia sonchifolia extract activity against white spot syndrome virus and yellow head virus in shrimp cell cultures. Dis Aquat Organ 2015; 115: 157-164
• 65 Sundaram D, Kesavan K, Kumaravel H, Mohammed RF, Tohru M, Toshiaki I, Raja S. Protective efficacy of active compounds from Phyllanthus amarus against white spot syndrome virus in freshwater crab (Paratelphusa hydrodomous). Aquac Res 2016; 47: 2061-2067
• 66 Dinesh S, Sudharsana S, Mohanapriya A, Itami T, Sudhakaran R. Molecular docking and simulation studies of Phyllanthus amarus phytocompounds against structural and nucleocapsid proteins of white spot syndrome virus. 3 Biotech 2017; 7: 353
• 67 Bindhu F, Velmurugan S, Donio MBS, Michaelbabu MV, Citarasu T. Influence of Agathi grandiflora active principles inhibit viral multiplication and stimulate immune system in Indian white shrimp Fenneropenaeus indicus against white spot syndrome virus infection. Fish Shellfish Immunol 2014; 41: 482-492
• 68 Palanikumar P, Daffni Benitta DJ, Lelin C, Thirumalaikumar E, Michaelbabu M, Citarasu T. Effect of Argemone mexicana active principles on inhibiting viral multiplication and stimulating immune system in Pacific white leg shrimp Litopenaeus vannamei against white spot syndrome virus. Fish Shellfish Immunol 2018; 75: 243-252
• 69 Muliani M, Susianingsih E. The effectiveness of methanol extract and fractionations from mangrove leaves Sonneratia alba and Bruguiera gymnorrhiza to prevent white spot syndrome virus (WSSV) infection in black tiger shrimp Penaeus monodon. J Akuakultur Indones 2018; 17: 43-52
• 70 Velmurugan S, Jerin N, Michael Babu M, Bindhu F, Albin Dhas S, Citarasu T. Screening and characterization of antiviral compounds from Enteromorpha flexuosa against white spot syndrome virus (WSSV) and its in vivo influence on Indian white shrimp Fenneropenaeus indicus. Aquacult Int 2015; 23: 65-80
• 71 Huang AG, Tu X, Qi XZ, Ling F, Zhu B, Wang GX. Gardenia jasminoides Ellis inhibit white spot syndrome virus replication in red swamp crayfish Procambarus clarkii. Aquaculture 2019; 504: 239-247
• 72 Huang AG, Tan XP, Qu SY, Wang GX, Zhu B. Evaluation on the antiviral activity of genipin against white spot syndrome virus in crayfish. Fish Shellfish Immunol 2019; 93: 380-386
• 73 Lupini C, Cecchinato M, Scagliarini A, Graziani R, Catelli E. In vitro antiviral activity of chestnut and quebracho woods extracts against avian reovirus and metapneumovirus. Res Vet Sci 2009; 87: 482-487
• 74 Barros AV, da Conceicao AO, Simoni IC, Padilla MA, Fernandes MJB, Arns CW. In vitro antiviral activity of seeds from Guettarda angelica against avian viruses. J Appl Pharm Sci 2013; 3: 31-33
• 75 Clark KJ, Grant PG, Sarr AB, Belakere JR, Swaggerty CL, Phillips TD, Woode GN. An in vitro study of theaflavins extracted from black tea to neutralize bovine rotavirus and bovine coronavirus infections. Vet Microbiol 1998; 63: 147-157
• 76 Mohajer Shojai T, Ghalyanchi Langeroudi A, Karimi V, Barin A, Sadri N. The effect of Allium sativum (garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg. Avicenna J Phytomed 2016; 6: 458-267
• 77 Chen CH, Zuckerman DM, Brantley S, Sharpe M, Childress K, Hoiczyk E, Pendleton AR. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet Res 2014; 10: 24
• 78 Zhang P, Liu XF, Liu HY, Wang WX, Liu XH, Li XT, Wu XH. Astragalus polysaccharides inhibit avian infectious bronchitis virus infection by regulating viral replication. Microb Pathog 2018; 114: 124-128
• 79 Aricapa Giraldo HJ, Salazar Salazar DF, Uribe S, Angel Isaza I. Inhibition of bird infectious bronchitis virus through the use of essential oils. REDVET 2017; 18: 101017
• 80 Ertürk Ö, Demirbag Z, Beldüz AO. Antiviral activity of some plant extracts on the replication of Autographa californica nuclear polyhedrosis virus. Turk J Biol 2000; 24: 833-844
• 81 Aurori AC, Bobiş O, Dezmirean DS, Mărghitaş LA, Erler SA. Bay laurel (Laurus nobilis) as potential antiviral treatment in naturally BQCV infected honeybees. Virus Res 2016; 222: 29-33
• 82 Schwerdtfeger SM, Melzig MF. Effects of plant extracts on neuraminidase activity. Zeitschr Phytother 2008; 29: 65-70
• 83 Bhanuprakash V, Hosamani M, Balamurugan V, Gandhale P, Naresh R, Swarup D, Singh RK. In vitro antiviral activity of plant extracts on goatpox Virus replication. Indian J Exp Biol 2008; 46: 120-127
• 84 Rasool A, Khan MU, Ali MA, Anjum AA, Ahmed I, Aslam A, Mustafa G, Masood S, Ali MA, Nawaz M. Anti-avian influenza virus H9N2 activity of aqueous extracts of Zingiber officinalis (ginger) and Allium sativum (garlic) in chick embryos. Pak J Pharm Sci 2017; 30: 1341-1344
• 85 Abd-Alla HI, Abu-Gabal NS, Hassan AZ, El-Safty MM, Shalaby NMM. Antiviral activity of Aloe hijazensis against some haemagglutinating viruses infection and its phytoconstituents. Arch Pharm Res 2012; 35: 1347-1354
• 86 Arora R, Singh S, Sharma RK. Neem Leaves. Indian herbal Medicine. In: Watson RR, Preedy VR. eds. Botanical Medicine in clinical Practice. Oxon: CABI; 2008: 94
• 87 Wafaa AH, Howaida IAA, Hassan A, El-Safty MM. Chemical composition and in vitro antiviral activity of Azadirachta indica A. Juss (Neem) leaves and fruits against Newcastle disease virus and infectious bursal disease virus. Aust J Basic Appl Sci 2007; 1: 801-812
• 88 Shaukat TM, Ashraf M, Omer MO, Rasheed MA, Muhammad K, Shaukat TM, Younus M, Shahzad MK. Comparative efficacy of various antiviral agents against avian influenza virus (type H7N3/Pakistan/2003). Pak J Zool 2011; 43: 849-854
• 89 Baatartsogt T, Bui VN, Trinh DQ, Yamaguchi E, Gronsang D, Thampaisarn R, Ogawa H, Imai K. High antiviral effects of hibiscus tea extract on the H5 subtypes of low and highly pathogenic avian influenza viruses. J Vet Med Sci 2016; 78: 1405-1411
• 90 Zaher SK, Ahmed WM, Sakina NZ. Observations on the biological effects of black cumin seed (Nigella sativa) and green tea (Camellia sinensis). Glob Vet 2008; 2: 198-204
• 91 Bhanuprakash V, Hosamani M, Balamurugan V, Singh RK, Swarup D. In-vitro antiviral activity of Eugenia jambolana plant extract on buffalopox virus: conventional and qPCR methods. Int J Trop Med 2007; 2: 3-9
• 92 Shome BR, Rajeswari Shome SN. Antiviral activity of latex from Excoecaria agallocha: a mangrove species from Andaman. Indian J Anim Health 1998; 37: 65-66
• 93 Kudi AC, Myint SH. Antiviral activity of some Nigerian medicinal plant extracts. J Ethnopharmacol 1999; 68: 289-294
• 94 Bombardelli E, Morazzoni P. Hypericum perforatum . In: Wynn SG, Fougére BJ. eds. Veterinary herbal Medicine. St. Louis, MO: Mosby Elsevier; 2007: 643
• 95 Lavie G, Valentine F, Levin B, Mazur Y, Gallo G, Lavie D, Weiner D, Meruelo D. Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. Proc Natl Acad Sci U S A 1989; 86: 5963-5967
• 96 Huang YD, Li YM, Xiang Q, Su Z, Wang LC, Li XK, Huang ZF. Antiviral effect on H5N1 avian influenza virus of compound of Curcuma zedoaria volatile oil and Hypericum perforatum extract liquid. J China Pharm Univ 2009; 40: 166-172
• 97 Pu XY, Liang JP, Wang XH, Hua LY, Liu Y. Inhibition of Hypericum perforatum extract on influenza A virus. Chin Trad Herb Drugs 2010; 41: 259-264
• 98 Yang Z, Wang Y, Zheng Z, Zhao S, Zhao J, Lin Q, Li C, Zhu Q, Zhong N. Antiviral activity of Isatis indigotica root-derived clemastanin B against human and avian influenza A and B viruses in vitro . Int J Mol Med 2013; 31: 867-873
• 99 Pourghanbari G, Nili H, Moattari A, Mohammadi A, Iraji A. Antiviral activity of the oseltamivir and Melissa officinalis L. essential oil against avian influenza A virus (H9N2). Virusdisease 2016; 27: 170-178
• 100 Haselmeyer A, Nowotny N, Heistinger H, Kolodziejek J, Homola J, Nöbauer K, Razzazi-Fazeli E, Soliman H, El-Matbouli M, Zitterl-Eglseer K. Melissa officinalis L. extract and its main phenolic compound rosmarinic acid as phytoprophylactic feed additives against koi herpesvirus infection in a pilot study. Wien Tierärztl Mschr 2018; 105: 175-183
• 101 Direkbusarakom S. Application of medicinal herbs to aquaculture in Asia. Walailak J Sci Technol 2004; 1: 7-14
• 102 Micol V, Caturla N, Pérez-Fons L, Más V, Pérez L, Estepa A. The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV). Antiviral Res 2005; 66: 129-136
• 103 Zaher SK. In vitro studies on the antiviral effect of olive leaf against Infectious Laryngotracheitis Virus. Glob Vet 2007; 1: 24-30
• 104 Blank DE, Correa RA, Freitag RA, Cleff MB, Oliveira Hübner S. Anti-equine arteritis virus activity of ethanolic extract and compounds from Origanum vulgare . Cienc Agr Londrina 2017; 38: 759-764
• 105 Blank DE, Oliveira Hübner S, Alves GH, Cardoso CAL, Freitag RA, Cleff MB. Chemical composition and antiviral effect of extracts of Origanum vulgare . Advan Biosci Biotechnol 2019; 10: 188-196
• 106 Sulaiman LK, Oladele OA, Shittu IA, Emikpe BO, Oladokun AT, Meseko CA. In-ovo evaluation of the antiviral activity of methanolic root-bark extract of the African Baobab (Adansonia digitata Lin.). Afr J Biotechnol 2011; 10: 4256-4258
• 107 Müller V, Chávez JH, Reginatto FH, Zucolotto SM, Niero R, Navarro D, Yunes RA, Schenkel EP, Barardi CR, Zanetti CR, Simões CM. Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies Virus. Phytother Res 2007; 21: 970-974
• 108 Waihenya RK, Mtambo MMA, Nkwengulila G. Evaluation of the efficacy of the crude extract of Aloe secundiflora in chickens experimentally infected with Newcastle disease virus. J Ethnopharmacol 2002; 79: 299-304
• 109 Waihenya RK, Keriko JM, Mtambo MMA, Nkwengulila G, Kayser O, Hafez HM. Antiviral activity of the crude extracts and phytochemical fractions of Aloe secundiflora against Newcastle disease virus. J Trop Microbiol Biotechnol 2005; 1: 10-13
• 110 Kohn LK, Queiroga CL, Martini MC, Barata LE, Porto PSS, Souza L, Arns CW. In vitro antiviral activity of Brazilian plants (Maytenus ilicifolia and Aniba rosaeodora) against bovine herpesvirus type 5 and avian Metapneumovirus. Pharm Biol 2012; 50: 1269-1275
• 111 Ayodele PO, Okonko IO, Odu NN, Banso A. Antiviral effect of Anthocleista nobilis root extract on the biochemical indices of poultry fowls infected with Newcastle disease virus (NDV). Annals Biol Res 2012; 3: 20-30
• 112 Liu Y, Yan GQ, Chen GH, Zhang J. Efficacy trials of crude extraction from Artemisia annua L. against Newcastle disease virus in vivo in Xinjiang. Mod Appl Sci 2009; 3: 176-178
• 113 Ruffa MJ, Wagner ML, Suriano M, Vicente C, Nadinic J, Pampuro S, Salomón H, Campos RH, Cavallaro L. Inhibitory effect of medicinal herbs against RNA and DNA viruses. Antivir Chem Chemother 2004; 15: 153-159
• 114 Fatima M, Zaidi NU, Amraiz D, Afzal F. In vitro antiviral activity of Cinnamomum cassia and its nanoparticles against H7N3 influenza A virus. J Microbiol Biotechnol 2016; 26: 151-159
• 115 Klaywong K, Khutrakul G, Choowongkomon K, Lekcharoensuk C, Petcharat N, Leckcharoensuk P, Ramasoota P. Screening for lead compounds and herbal extracts with potential anti-influenza viral activity. Southeast Asian J Trop Med Public Health 2014; 45: 62-74
• 116 Umar S, Shah MAA, Munir MT, Yaqoob M, Fiaz M, Anjum S, Kaboudi K, Bouzouaia M, Younus M, Nisa Q, Iqbal M, Umar W. Synergistic effects of thymoquinone and curcumin on immune response and anti-viral activity against avian influenza virus (H9N2) in turkeys. Poult Sci 2016; 95: 1513-1520
• 117 Felipe AMM, Rincão VP, Benati FJ, Linhares REC, Galina KJ, De Toledo CEM, Lopes GC, De Mello JCP, Nozawa C. Antiviral effect of Guazuma ulmifolia and Stryphnodendron adstringens on poliovirus and Bovine herpesvirus. Biol Pharm Bull 2006; 29: 1092-1095
• 118 Buckwold VE, Wilson RJH, Nalca A, Beer BB, Voss TG, Turpin JA, Buckheit RW, Wei JY, Wenzel-Mathers M, Walton EM, Smith RJ, Pallansch M, Ward P, Wells J, Chuvala L, Sloane S, Paulman R, Russell J, Hartman T, Ptak R. Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral Res 2004; 61: 57-62
• 119 Pliego Zamora A, Edmonds JH, Reynolds MJ, Khromykh AA, Ralph SJ. The in vitro and in vivo antiviral properties of combined monoterpene alcohols against West Nile virus infection. Virology 2016; 495: 18-32
• 120 Herrmann EC, Kucera LS. Antiviral substances in plants of the Mint family (Labiatae). III. Peppermint (Mentha piperita) and other mint plants. Proc Soc Exp Biol Med 1967; 124: 874-878
• 121 Chollom SC, Olawuyi AK, Danjuma LD, Nanbol LD, Makinde IO, Hashimu GA, Alesa MU, Esilonu JT, Ogundeji EB, Kwatjel JS. Antiviral potential of aqueous extracts of some parts of Momordica balsamina plant against Newcastle disease virus. J Adv Pharm Technol Res 2012; 2: 82-92
• 122 Chollom SC, Agada GOA, Gotep IG, Mwankon SE, Dus PC, Bot YS, Nyango DY, Singnap CL, Fyaktu EJ, Okwori AEJ. Investigation of aqueous extract of Moringa oleifera Iam seed for antiviral activity against Newcastle disease virus in ovo . J Med Plants Res 2012; 6: 3870-3875
• 123 Eze DC, Okwor EC, Osita AOJ, Nnabuike OD, Olu SSV. Effects of Moringa oleifera methanolic leaf extract on the morbidity and mortality of chickens experimentally infected with Newcastle disease virus (Kudu 113) strain. J Med Plants Res 2012; 6: 4443-4449
• 124 Mochida K. Anti-influenza virus activity of Myrica rubra leaf ethanol extract evaluated using Madino-Darby canine kidney (MDCK) cells. Biosci Biotechnol Biochem 2008; 72: 3018-3020
• 125 Ooi LSM, Tian L, Su M, Ho WS, Sun SS, Chung HY, Wong HN, Ooi VE. Isolation, characterization, molecular cloning and modeling of a new lipid transfer protein with antiviral and antiproliferative activities from Narcissus tazetta . Peptides 2008; 29: 2101-2109
• 126 Jayati AK, Bhatia A, Kumar A, Goel A, Gupta S, Rahal A. In vitro antiviral potential of Ocimum sanctum leaves extract against Newcastle disease virus of poultry. Int J Microbiol Immunol Res 2013; 2: 51-55
• 127 Ahmad A, Davies J, Randall S, Skinner GRB. Antiviral properties of extract of Opuntia streptacantha . Antiviral Res 1996; 30: 75-85
• 128 Ooi LSM, Sun SSM, Ooi VEC. Purification and characterization of a new antiviral protein from the leaves of Pandanus amaryllifolius (Pandanaceae). Int J Biochem Cell Biol 2004; 36: 1440-1446
• 129 Yang CH, Tan DH, Hsu WL, Jong TT, Wen CL, Hsu SL, Chang PC. Anti-influenza virus activity of the ethanolic extract from Peperomia sui . J Ethnopharmacol 2014; 155: 320-325
• 130 Chollom SC, Agada GOA, Bot DY, Okolo MO, Dantong DD, Choji TP, Echeonwu BC, Bigwan EI, Lokason S, Banwat E. Phytochemical analysis and antiviral potential of aqueous leaf extract of Psidium guajava against Newcastle disease virus in ovo . J App Pharm Sci 2012; 2: 45-49
• 131 Kim JH, Ryu YB, Kang NS, Lee BW, Heo JS, Jeong IY, Park KH. Glycosidase inhibitory flavonoids from Sophora flavescens . Biol Pharm Bull 2006; 29: 302-305
• 132 Ibrahim AK, Youssef AI, Arafa AS, Foad R, Radwan MM, Ross S, Hassanean HA, Ahmed SA. Anti-H5N1 virus new diglyceride ester from the Red Sea grass Thallasodendron ciliatum . Nat Prod Res 2013; 27: 1625-1632
• 133 Kamei M, Nishimura H, Takahashi T, Takahashi N, Inokuchi K, Mato T, Takahashi K. Anti-influenza virus effects of cocoa. J Sci Food Agric 2016; 96: 1150-1158
• 134 Haetrakul T, Sritularak B, Chansue N. Clinacanthus nutans (Burm.f.) Lindau extract against Cyprinid herpesvirus 3 in koi fin cell line. J Mahanakorn Vet Med 2016; 11: 115-124
• 135 Haetrakul T, Dunbar SG, Chansue N. Antiviral activities of Clinacanthus nutans (Burm.f.) Lindau extract against Cyprinid herpesvirus 3 in koi (Cyprinus carpio koi). J Fish Dis 2018; 41: 581-587

Publication History

Received: 31 January 2020

Accepted after revision: 21 July 2020

Article published online:
10 August 2020