Keywords

1 Introduction

Viruses are the tiny entities too small to be seen by an ordinary light microscope. The structure of viruses consists of single or double stranded nucleic acids such as ribonucleic acid or deoxyribonucleic acid, surrounded by protein capsid. The interesting fact about viruses is that viruses only survive and replicate inside a living organism [1]. Host cell defense mechanism is the only responsible factor for the survival of the virus [2]. In the initial stage, more than one virion entered into the host cell followed by interaction with host defense and using tropism behavior it can easily travel toward the susceptible tissue and cause infection by multiple replications [3].

Based on the structure, viruses are divided into helical, icosahedral, spherical types and as per the chemical composition viruses are mainly of two types such as ribonucleic acid virus and deoxyribonucleic acid virus with single strand or double strand [4].

Based on the type of host, viruses are further categorized into plant virus, animal virus, and bacteriophage.

1.1 Plant Virus

Plant viruses directly affect the plant species and cause economic depletion. Based on the family and genera, plant viruses are divided into single stranded DNA virus, double stranded DNA virus, double stranded RNA virus, positive single stranded RNA virus, and negative single stranded RNA virus. Caulimoviridae (Caulimovirus, Petuvirus, Soymovirus, Badnavirus) and Geminiviridae (Mastrevirus, Curtovirus, Topocuvirus) belong to single stranded and double stranded DNA viruses. Reoviridae (Fijivirus, Oryzavirus) and Partitiviridae (Alphacryptovirus) belong to double stranded RNA virus. Bunyaviridae (Tospovirus) and Rhabdoviridae (Cytorhabdovirus) belong to negative single stranded RNA virus. Bromoviridae (Bromovirus), Luteoviridae (Sobemovirus), and Comoviridae (Idaeovirus) belong to positive single stranded RNA virus.

1.2 Animal Virus

Animal viruses are mainly associated with pathogenesis of different viral diseases. Animal viruses are classified into single and double stranded DNA virus, single stranded (negative and positive) RNA virus, and double stranded RNA virus. Parvovirus, Polyomavirus, Papillomavirus, Adenovirus, Herpesvirus belong to single and double stranded DNA virus, respectively. Picornavirus, Flavivirus, Togavirus, and Coronavirus belong to positive single stranded RNA virus. Rhabdovirus, Orthomyxovirus, and Paramyxovirus belong to negative single stranded RNA virus. Reovirus belongs to double stranded DNA virus.

1.3 Bacteriophage

Bacteriophage (phagevirusis) replicated in bacterial cellular system. Nucleic acid genome of bacteriophage is protected within a capsid protein shell. Bacteriophage helps to encode various deadly bacterial toxins. Antimicrobial resistant genes are the vectors for genetic material transfer.

2 Plant Metabolites

In the present scenario, for management of human health and betterment of mankind, plant materials are playing the most important role. The greater efficacy and minimal side effects are unique selling points of plant materials. But maximum medicines are allopathic and most of them consist of synthetic chemical. These synthetic molecules are observed with marked adverse and side effects. Natural products such as alkaloids, glycosides, terpenoids, and flavonoids are mostly required for human health and immune response [5]. Natural products help to build and strengthen human mind and body to fight against various viral manifestations. Plant metabolites are the compounds produced by the metabolism of plants. Metabolites are the organic compounds produced by enzymatic chemical reactions [6]. Plant metabolites are divided into two types: primary and secondary metabolites [7].

2.1 Primary Metabolite

Primary metabolite directly participated in the growth, development, and reproduction. Primary metabolites are present in all living organisms and cells. Primary metabolites are the intrinsic parts of human biological functions such as amino acids, deoxyribonucleic acid, ribonucleic acid, and so on. Primary metabolites are produced by metabolism and biotransformation of carbohydrates, proteins, fatty acids, and lipids using various enzymes. Primary metabolites are lactic acid, pyruvic acid, ethanol, arachidonic acid, prostaglandin, leukotriene, malic acid, fumaric acid, ketone bodies and pyridine, pyrimidine nucleotides, vitamins, and so on [8].

2.2 Secondary Metabolite

Secondary metabolites do not directly participate in growth, development, and reproduction of organisms. These are organic compounds produced to aim in normal growth and development. They are biosynthetically obtained from primary metabolites. Secondary metabolites are mainly pollinator attractants and provide protection against various chemical and environmental stresses. Secondary metabolites are the organic compounds developed by the plants from the attacks of herbivores and pathogens. They increase the reproduction capability of plants under diverse condition. Some secondary metabolites help to produce good color substance and odor to attract animals for the exchange of pollens to facilitate reproduction. Terpenes, phenolic compounds, and nitrogen containing compounds are the types of secondary metabolites [9]. Terpenes (limonene, menthol, etc.) are produced from pyruvate and 3-phosphoglycerate using methyl erythritol pathway and mevalonic acid pathways. Phenolic compounds (Azadirachtin, α-Ecdysone, anthocyanin, anthocyanidin, caffeic acid, ferulic acid, psoralen, etc.) are obtained from acetyl coenzyme-A, phosphoenolpyruvate, and aromatic amino acids via malonic acid and shikimic acid pathways. Nitrogen compounds (alkaloids: nicotine, atropine, morphine, codeine, strychnine, caffeine, etc.) are obtained from aliphatic and aromatic amino acids by shikimic acid pathway [10].

2.2.1 Terpenes

Terpenes are one of the secondary metabolites. Terpenes consist of isoprene units (C5H8). Terpenes are divided into six types such as monoterpenes (C10H16), sesquiterpenes (C15H24), diterpenes (C20H32), triterpenes (C30H48), tetraterpenes (C40H64), and polyterpenoids (more than eight isoprene subunits) [14]. The terpenes are synthesized by methyl erythritol phosphate and mevalonic acid pathways. In the methyl erythritol phosphate pathway, pyruvate and glyceraldehyde-3-phosphate are combined to generate isopentenyl diphosphate unit, which further produces geranyl pyrophosphate and di/tetra terpenes. As per the mevalonic acid pathway, sesquiterpene and triterpene are developed from acetyl coenzyme-A via 3-hydroxy-3-methylglutaryl coenzyme A [11].

2.2.2 Phenolic Compounds

Phenolic compounds are the compounds with phenol (aromatic hydroxyl) group in its structure. Shikimic acid pathway and malonic acid pathway are the main ways to develop various phenolic compounds [12]. Simple phenolic compounds, lignin, condensed tannin, hydrolysable tannin, and flavonoids are the most common types of phenolic compounds. Phosphoenolpyruvate as obtained from glycolysis is the source material for the synthesis of these phenolic compounds via phenylalanine, gallic acid, and acetyl coenzyme A (malonic acid pathway). In the biosynthesis of flavonoid and anthocyanin, starting material phenylalanine was reacted with phenylalanine ammonia lyase to form coumarin, flavones, isoflavones, flavonols, flavonone, and anthocyanin. Caffeic acid and ferulic acid are the simple phenylpropanoid; psoralen is the example of coumarin; vanillin and salicylic acids are the examples of benzoic acid derivatives [13].

2.2.3 Nitrogenous Compounds

Among nitrogenous compounds alkaloids, cyanogenic glycosides, glucosinolates, and nonprotein amino acids are the principal types.

Alkaloids are the nitrogenous compounds synthesized from lysine, tryptophan, and tyrosine amino acids. There are seven types of alkaloids such as: pyrrolidine (nicotine generated from aspartic acid), tropane (atropine obtained from ornithine), piperidine (coniine from lysine), pyrrolizidine (retrorsine obtained from ornithine), quinolizidine (lupinine obtained from lysine), isoquinoline (codeine, morphine obtained from tyrosine), and indole (reserpine, strychnine obtained from tryptophan). Nicotinic acid and nicotine are obtained from ornithine via N-methyl pyrrolinium. One important example is senecionine (obtained from ragwort), where the non-toxic N-oxide form of senecionine is stored in plants and transformed into toxic tertiary alkaloid of senecionine within the digestive system of herbivores [14]. Most of the plant species contained alkaloids as principal component. Alkaloids are composed of variable chemical structures. Alkaloids are mainly nitrogenous compounds obtained from ammonia, which is mainly colorless, non-volatile solid in nature and bitter in taste.

Glycosides were those compounds which were yielded with one or more sugars after hydrolysis. Glycoside was composed of the sugar and the aglycone parts. The aglycone part of glycoside comprises terpene, flavonoid, coumarine, or other natural products. Among the sugars part found in natural glycosides, D-glucose was the most abundant one. L-rhamnose and L-fructose were found quite frequently. Among the pentose sugars, L-arabinose was more common than D-xylose. Due to the cyclic structure of the sugar moiety, two diastereoisomers were present depending on the configuration of the anomeric carbon. These diastereoisomers were called anomers and they were designated as α and β. This classification of glycosides depends upon the glycosidic linkage such as α and β as above the linkage was β configuration and below the linkage was α configuration. Chemically, glycosides are usually mixed acetals with hydroxyl (OH−) group on the anomeric carbon which is substituted by nucleophilic atom. Glycone part of glycoside was joined to the aglycone part via oxygen atom (known as O-glycosides), carbon atom (known as C-glycosides), nitrogen atom (known as N-glycosides), and sulfur atom (known as S-glycosides). Cyanogenic glycosides and glucosinolate are the interesting nitrogenous compounds. Plants with cyanogenic glycoside are normal in nature but when it is ruptured, it produces toxic hydrogen cyanide. Cyanogenic glycosides are glycoside with cyano group. Cyanogenic glycosides are breakdown into cyanohydrin by glycosidase enzyme (which breakdowns the glycosidic linkage) followed by reaction with hydroxynitrile lyase to form ketone body and hydrogen cyanide [15]. On the other hand, glucosinolate produces smell of sulfur due to production of isothiocyante which protects the plant from herbivores. Glucosinolate produces isothiocyanate and nitrile compounds after interaction with thioglucosidase enzyme and upon spontaneous reaction to produce sulfur dioxide. Cabbage, broccoli, and radish contained this type of secondary metabolite [16].

Non-protein amino acids are the natural molecules which look like amino acid but produce toxic effect after metabolism. This single change in the structure developed the new structure, which blocks the transcription process [17]. Existence of mankind depends upon plants kingdom. They are the primary source of minerals, vitamins, and other essential nutrients. Phytoconstituents are always preferable due to their biosafe bioactivity profile. The diversified flora of tropical, sub-tropical, and Himalayan regions is the primary source of phytoconstituents. But in this time population density, pollution, and over ambitious energy projects push the natural source into an endangered species. Primary plant metabolites are used for growth, defense, and pollination. Secondary metabolites have tremendous medicinal values to treat or mitigate a disease condition. In this scenario, biotechnological approaches like tissue culture, clonal propagation, hairy root culture, callus formation, and gentic mutation come as savior.

Most of the plant metabolites are mainly categorized into five categories such as polyphenols, alkaloids, saponins, terpenoids, and carbohydrates. Most of the metabolites belong to Acanthaceae, Adoxaceae, Amaranthaceae, Anacardiaceae, Myristicaceae, Araceae, Asterceae, Fabaceae, Berberidaceae, Combretaceae, Euphorbiaceae, Geraniaceae, Lamiaceae, Moraceae, Phyllanthaceae, Rosaceae, Rutaceae, Zingiberaceae, Polygonaceae plant families. This chapter mainly highlighted the importance of various medicinal plants and their metabolites to conquer viral manifestations.

3 Plant with Anti-Viral Properties

3.1 Plants Showing Anti-HIV Properties

Nutan et al. suggested the efficient role of Acacia catechu plant in the treatment of human immunodeficiency virus by inhibiting the activity of human protease enzyme and Tat protein. Acacia catechu (also known as Khair) belongs to the family Fabaceae (Leguminosae). It consists of catechin, epicatechin, epicatechin gallate, procatechinic acid, tannins, alkaloids quercetin, and kaempferol, porifera sterol glucosides, (+)-afzelechin gum are also present in minor quantity. When HIV-1 virus interacted with different receptor and protein such as chemokine receptor5, glycoprotein for T cell receptor (CD4), and T cell coreceptor (play an important role in the binding of HIV virion), it enters inside the cell and then use HIV-1 integrase and reverse transcriptase enzymes to make the virus transcribed. In this way, Tat protein responsive element plays an essential role in the replication of the virus. In the treatment of the replication of human immunodeficiency virus, Acacia catechu plays an important role. Acacia catechu contains various secondary metabolites such as 4-hydroxybenzoic acid (1), kaempferol (2), quercetin (3), 3,4′,7-trihydroxyl-3′,5-dimethoxyflavone (4), catechin (5), rutin (6), isorhamnetin (7), epicatechin (8), afzelechin (9), epiafzelechin (10), mesquitol (11), ophioglonin (12), aromadendrin (13), and phenol (14). Three extracts of Acacia catechu such as 50% ethanolic extract, aqueous extract, and n-butanol extract with different concentrations (0.1 μg/ml, 0.5 μg/ml, 2.0 μg/ml, 5.0 μg/ml, and 10 μg/ml) were applied into human immunodeficiency virus (11IN1290SJ and 17MT14) infected TZM-bl cells (generated from HeLa cell line) as compared to zidovudine to access luminescence activity, percent inhibition of human immunodeficiency protease activity with different extracts of Acacia catechu as compared to saquinavir and percent inhibition of Tat protein was evaluated using different concentrations of n-butanol fraction. Outcomes revealed that aqueous, ethanolic (50%), and n-butanol extracts of the plant were observed with inhibitory concentrations (50%) of 1.8 μg/ml, 3.6 μg/ml and 1.7 μg/ml, respectively, as well as 12.9 μg/ml of inhibitory concentrations (50%) against human immunodeficiency virus-1 protease enzyme. Among all the secondary metabolites, only catechin showed greater inhibitions against human immunodeficiency virus-1 with inhibitory concentration (50%) 0.60 μg/ml. These data confirmed the importance of Acacia catechu plant in the management of human immunodeficiency virus manifestation [18].

figure a

Huang et al. highlighted the importance of olive leaf extracts in the treatment of human immunodeficiency virus disease. In this work, aqueous extract of olive leaves was prepared, followed by purification with water and acetonitrile (79.21) to extract verbascoside:0.38% (15), luteolin-7-glucoside:0.68% (16), apigenin-7-glucoside: 0.18% (17), oleuropein:12.8% (18), and oleuroside:0.51% (15). Then H9 cells (clone of Hut 78 cell line) were used to infect human immunodeficiency virus  and thus were used to evaluate the anti-viral efficacy against human immunodeficiency virus. Outcomes showed compounds 18 and 19 observed with marked inhibition of viral mitigation. These data confirmed the role of olive leaf extract in the treatment of human immunodeficiency virus infection [19].

figure b

Behbahani et al. suggested the role of methanolic extracts of aerial parts of Ocimum basilicum and field dodder Cuscuta campestris in the management of human immunodeficiency virus type-1 infection. In this statement, basil plant was extracted with the mobile phase composed of hexane, acetone, and methanol in the ratio of 8:2:0 to 0:4:6 followed by chromatographic separation using different ratios (2:1, 1:1 and 1:2) of ethylacetate and methanol. This procedure eluted eugenol (20) as active constituent. Another experiment was with field dodder Cuscuta campestris, which was extracted with same ratios of hexane, acetone, and methanol followed by chromatographic separation with different concentrations of ethylacetate and methanol (3:1, 2:1 and 1:1) to isolate eugenol and eugenol epoxide as chemical constituents. Then different concentrations (50 μg/ml, 100 μg/ml, 250 μg/ml, and 500 μg/ml) of eugenol and eugenol epoxide were tested against human immunodeficiency virus type-1 strain with the comparison of zidovudine. Outcomes revealed that 50% of the total viral strains were inhibited by eugenol and eugenol epoxide with 350 μg/ml and 80 μg/ml, respectively. This information confirmed the role of basil and field dodder parasite in the treatment of human immunodeficiency virus [20].

figure c

Estari et al. confirmed the role of Phyllanthus emblica plant in the management of acquired immune deficiency syndrome. In this context, different extracts (n-hexane, carbon tetrachloride, chloroform, and aqueous) of the Phyllanthus emblica at different concentrations (0.02 mg/ml, 0.04 mg/ml, 0.09 mg/ml, 0.18 mg/ml, 0.37 mg/ml, 0.75 mg/ml, and 1.5 mg/ml) were used to evaluate cell toxicity using peripheral blood mononuclear cells (obtained from ficoll-hypaque density gradient centrifugation technique) and anti-human immunodeficiency virus reverse transcriptase enzyme. Outcomes showed that different extracts of n-hexane, carbon tetrachloride, chloroform, and aqueous are observed with 1.8%, 2.9%, 1.6%, and 0.8%, respectively. It was also observed that upto 0.75 mg/ml concentrations, all the cells were viable as well as aqueous fraction was non-toxic in nature even at 1.5 mg/ml concentration. Anti-viral activities of different fractions of the plant showed maximum inhibitions at 0.12 mg/ml (carbon tetrachloride fraction) and 0.5 mg/ml (chloroform fraction) concentrations, respectively. These data stated the importance of Phyllanthus emblica plant in the management of acquired immune deficiency syndrome [21].

Notka et al. confirmed the importance of Phyllanthus amarus in the treatment of human immunodeficiency virus. In this work, water/alcohol extract, gallotannin fraction of the plant, geraniin (21), and corilagin (22) were used to evaluate the inhibitions of human immunodeficiency virus in terms of CD4 (co receptor of T cell receptor)-gp120 (envelope glycoprotein-120) along with inhibitions of reverse transcriptase, integrase, and protease enzymes. Outcomes showed that geraniin showed maximum inhibitions of human immunodeficiency virus in terms of CD4 (co-receptor of T cell receptor)-gp120 (envelope glycoprotein-120) along with inhibitions of reverse transcriptase, integrase, and protease enzymes with 50% inhibitory concentration values 0.48 μg/ml, 2.53 μg/ml, 0.16 μg/ml, and 6.28 μg/ml, respectively. These data confirmed the anti-human immunodeficiency virus activity of Phyllanthus amarus extract [22].

figure d

Abd-Elazem et al. expressed the importance of aqueous extract of Salvia miltiorrhiza plant and M522 [lithospermic acid (23)] and M532 [lithospermic acid B (24)] in the inhibition of human immunodeficiency virus type-1 integrase enzyme. Data said that lithospheric acid and lithospermic acid B inhibited the integrase enzyme with 0.83 micromolar and 0.48 micromolar concentrations, respectively. Human immunodeficiency virus integrase catalytic target deoxyribonucleic acid was observed with remarkable inhibitions by both lithospermic acid and lithospermic acid B with inhibitory concentration values 0.48 micromolar and 0.37 micromolar concentrations, respectively. These experimental data confirmed the importance of danshen in the treatment of acquired immune deficiency syndrome [23].

figure e

Bessong et al. showed the anti-viral activities of aqueous and methanol extracts of Bridelia micrantha (stem), Combretum mole (stem-bark), and Terminalia sericea (leaves) against ribonucleic acid dependent deoxyribonucleic acid polymerase enzyme and ribonuclease H enzyme inhibitions associated with reverse transcriptase enzyme of human immunodeficiency virus infection. Outcomes revealed that 50% inhibitory concentrations of aqueous and methanol extracts of Bridelia micrantha were 34.6 μg/ml, 23.5 μg/ml, and 27.9 μg/ml, 18.9 μg/ml; Combretum mole were 81.3 μg/ml, 20.3 μg/ml and 79.1 μg/ml, 21.6 μg/ml; Terminalia sericea were 24.1 μg/ml, 7.2 μg/ml and 18.5 μg/ml, 8.1 μg/ml. These data confirmed that methanolic extract of Terminalia sericea showed good activity against acquired immune deficiency syndrome [24].

3.2 Plants with Anti-HSV Activity

Montanha et al. suggested the anti-viral efficacies of some Brazilian plants (Ilex brevicuspisReiss., Ilex theezans Mart., Baccharis erioclada DC., Baccharis megapotamica Hook. &Arn., Baccharis uncinella DC., Maytenusilicifolia, Glechonmarifolia, Glechon spathulate, Aloysia gratissima) against HSV. Aqueous extracts of Ilex brevicuspisReiss., Ilex theezansMart., Baccharis eriocladaDC., Maytenusilicifoliaand hydroethanolic extracts of Baccharis eriocladaDC., Baccharis megapotamicaHook. &Arn., Baccharis uncinellaDC., Maytenusilicifolia, Glechonmarifolia, Glechon spathulate, Aloysia gratissima were used and evaluated against KOS, ATCC-VR733 and 29 R-acyclovir resistant strains of HSV-1. Outcomes showed that Baccharis megapotamica was active against KOS strain of HSV with 0.0048 mg/ml concentration; Ilex theezans Mart. and Glechonspathulata showed maximum ATCC-VR733 strains of HSV with 0.25 mg/ml concentration respectively and Glechonspathulata observed with maximum effectivity against acyclovir resistant HSV with 0.25 mg/ml concentration as well as maximum cytotoxicity concentration (50%) was observed with Baccharis megapotamica with 0.0097 mg/ml concentration. Baccharis megapotamica belongs to Asteraceae. It consisted of spathulenol and caryophyllene oxide in the essential oil of the plant Ilex theezans belongs to Aquifoliaceae family with arbutin and dicaffeoylquinic acid as chemical constituents. Glechonspathulata belongs to Lamiaceae with β-caryophyllene and bicyclogermacrene as main constituents. These data stated the importance of some Brazilian plants against HSV infection [25].

Farahani et al. confirmed the importance of Camellia sinesis, Echium amoenum, and Nerium oleander against HSV. Camellia sinesis belongs to Theaceae with(−)-epigallocatechin,(−)-epigallocatechin gallate,(−)-epicatechin gallate, and(−)-epicatechin as principal chemical constituents. Echium amoenumplant belongs to Boraginaceae and rosamarinic acid, anthocyanidine, saponin, and terpoinds are present as main chemical constituents. Nerium oleander plant belongs to Apocynaceae family, which contained various cardiac glycosides such as oleandrin, gentiobiosyl oleandrin, odoroside. Aqueous extracts of Camellia sinesis, Echium amoenum, and Nerium oleander plants were tested against Hep-2 cell line (associated with laryngeal carcinoma) and HSV. Outcomes showed that Nerium oleander was observed with maximum toxicity against Hep-2 cell line with more than 50 μg/ml concentration as well as maximum anti-HSV was observed with Camellia sinesis with 20 μg/ml concentrations. These information confirmed the role of Camellia sinesis and Nerium oleander against the infection of HSV [26].

Allahverdiyev et al, explained the role of Melissa officinalis volatile oils in the treatment of HSV infection. In lemon balm, various volatile oils such as: 1-hepten-3-ol (25), 6-methyl-5-hepten-2-one (26), beta ocimene (27), linalool (28), nonanal (29), citronellal (30), neral (31), geraniol (32), pinocamphone (33), geranial (34), alpha-copaene (35), alpha-cubebene (36), elemene (37), caryophyllene (38), bisabolene (39), cedrene (40), calarene (41), cadinene (42), nerolidol (43), and cadinol (44) were present. In this context the anti-viral activity of lemon balm volatile oils (25 μg/ml, 50 μg/ml, 100 μg/ml, 150 μg/ml, and 200 μg/ml), cell toxicity assessment against Hep-2 cells (cell line linked to laryngeal carcinoma) and inhibition of HSV-2 is significant in comparison to acyclovir. Outcomes showed that number of viable cells were decreased with increasing concentration of volatile oils as well as percent inhibition of volatile oils against HSV-2 virulency was also remarkable. This data stated the importance of Melissa officinalis in the treatment of HSV type-2 strain [27].

figure f

Bag et al. suggested the importance of Mallotus peltatus in the treatment of HSV. In this work, various extracts of the plant (petroleum ether, chloroform; chloroform, methanol and crude methanol at different ratios) were prepared, followed by purification with petroleum ether and chloroform (1:1 ratio) and chloroform and methanol (95:5 ratio). After the extraction, two fractions (fraction A and fraction B) and ursolic acid (45) were obtained. Then these fractions were evaluated by cell toxicity using Vero cell and anti-viral assessments against HSV (type 1 and 2). Outcomes revealed that fraction A was observed with remarkable cell toxicity behavior against both the strains with effective concentration50 values 7.8 μg/ml and 8.2 μg/ml as compared to acyclovir (effective concentration50: 2.1 μg/ml and 2.9 μg/ml), respectively. As well as, in case of anti-viral study data, fraction A and ursolic acid at concentration 15 μg/ml showed similar inhibitions against two strains of HSV as acyclovir. These data confirmed the importance of Mallotus peltatus in the management of herpes infection [28].

figure g

Schuhmacher et al. suggested the importance of peppermint oil in the treatment of HSV. Peppermint oil consists of menthol (46), menthone (47), isomenthone (48), menthylacetate (49), cineole (50), limonene (51), and carvone (52) with 42.8%, 14.6%, 5.9%, 4.4%, 3.8%, 1.2%, and 0.6% weight/volume concentrations. African green monkey kidney cells (RC-37) were used to assess the cell toxicity and anti-viral activities. Outcomes showed that 0.014% concentration of peppermint oil was observed with marked cell toxicity data and after two hours of treatment with peppermint oil observed with 98% inhibition of HSV as well as acyclovir resistant HSV-1 inhibited by the oil and reduced by 99%. These data stated the importance of peppermint oil in the treatment of HSV [29].

figure h

Cheng et al. established the role of Phyllanthus urinaria plant in the treatment of HSV. Then the plant was extracted with a solvent mixture (acetone:water:4:1) followed by different ratios of water: methanol and water: acetone to yield the active constituent excoecarianin (53) (yield:0.001%). Then the active constituent was evaluated by cell toxicity assessment with vero cell using Sodium 3′-[1-(phenylaminocarbonyl)-3, 4-tetrazolium]-bis (4-methoxy-6-nitro) benzenesulfonic acid assay procedure and anti-viral efficacies against HSV-2 strain using vero cells treated with 100 plaque forming units of the virus. Different concentrations of excoecarianin such as 0 micromolar, 1 micromolar, 5 micromolar, 10 micromolar, 20 micromolar, 25 micromolar, 50 micromolar and 0.1 micromolar, 0.5 micromolar, 1 micromolar, 1.5 micromolar, 2 micromolar, 2.5 micromolar, 4 micromolar were used in the evaluation of cell toxicity and anti-viral efficacy of the molecule as compared with acyclovir. Outcomes revealed that at 1.4 micromolar concentration excoecarianin was observed with greater activity against the HSV. These data confirmed the role of the plant in the treatment of herpes simplex infection [30].

figure i

Reichling et al. confirmed the role of Rhus aromatica plant in the treatment of herpes infection. Aqueous extracts of stem, root, and bark of dry fragment sumac consist of tannin, gallic acid (54), quercetin, quercitrin (55), beta sitosterin (56), geranyl acetone (57), alpha ambrinol (58), and farnesyl acetone (59). Then different concentrations of extracts (0.00005%, 0.0001%, 0.00025%, 0.0005%, 0.00075%, 0.001%, 0.005%, 0.01%, 0.05%, 0.10%, and 0.25%) were experimented against type 1 and 2 strains of HSV in terms of percent plaque forming unit. Outcomes revealed that inhibitory concentration of the extract against HSV-1 and 2 is 0.0005% and 0.0043%, respectively with selectivity index values of 5400 and 628 associated with type 1 and 2 strains of the virus. These data confirmed the role of Rhus aromatica in the treatment of infection caused HSV [31].

figure j

AL-Megrin et al, suggested the importance of Rosmarinus officinalis plant in the treatment of HSV infection. In this work, aqueous extract of Rosmarinus officinalis plant was evaluated in the inhibition of HSV, where confluent cells were adsorbed with 100 plaque forming units of HSV-1 and 2, stained by naphthol black. Outcomes revealed that at 30 μg/ml and 40 μg/ml concentrations of the plant observed with 55% and 65% inhibitions of herpes simplex virus type 1 and 2 strains as well as at 50 μg/ml concentration of plant extract showed maximum inhibitions in both strains of HSV. These data stated the importance of Rosmarinus officinalis plant in the treatment of HSV [32].

Verma et al. expressed the role of Swertia chirata plant in the treatment of HSV infection. Aqueous extract of chirata plant and its diluted solution (1:64 ratio) were observed with 2 × 104plaque forming unit to the HSV treated vero cell and 15 × 104 plaque forming unit associated with non-treated cells, whereas acyclovir showed 15 × 104 plaque forming unit for non-treated vero cell and zero plaque forming unit associated with virus treated vero cell. These data stated the importance of Swertia chirata for the inhibition of HSV causing infection [33].

3.3 Plant Active Against Both Influenza and HSV

Alim et al. confirmed the role of different extracts (hexane, dichloromethane, and methanol) of Salvia cedronella against influenza and HSV grown on Madin-Darby canine kidney cells. Outcomes showed that hexane and methanol extracts observed with greater inhibitions against influenza virus (effective concentrations 50% = 0.25 mg/ml and 0.30 mg/ml) as compared with rimantadine hydrochloride as reference compound, whereas only methanolic extract showed good inhibition against herpes simplex virus (effective concentration 50% = 0.60 mg/ml) as compared to E)-5-(2-bromovinyl)-2′-deoxyuridine as reference compound. These data stated the anti-influenza and anti-herpes activities of Salvia cedronella [34].

3.4 Plant Active Against Hepatitis B Virus

Parvez et al. confirmed the role of nutgrass (Cyperus rotundus) in the treatment of hepatitis B virus. In this context, hexane, chloroform, ethyl acetate, n-butanol, and aqueous extracts of Cyperus rotundus were used to evaluate the hepatoprotective efficiency using MTT assay. Cyperus rotundus also known as nutgrass belongs to Cyperaceae family, which consists of cyperene and sitosterol. This activity showed that hexane, chloroform, and ethyl acetate extracts of Cyperus rotundus show maximum cell toxicity activities as compared to 2.7-dichlorofluorescein dye (used for the assessment of reactive oxygen species) with 389.5 μg/ml, 360.5 μg/ml and 470 μg/ml, respectively. Then dose dependent and time course of anti-hepatitis B virus activities were evaluated against the five extractions of Cyperus rotundus. Outcomes revealed that ethyl acetate, n-butanol, and aqueous extractions of Cyperus rotundus plant were observed with remarkable inhibitory activities (46.2 μg/ml, 94.8 μg/ml and 107.8 μg/ml, respectively). These data confirmed the role of Cyperus rotundus plant in the management of hepatitis B virus [35].

Yang et al. confirmed the role of dandelion and taraxasterol (60) (obtained from Taraxacum officinale) in the management of hepatitis B virus. In this way, HepG2 cell (hepatocellular carcinoma) was used. Cell toxicity against HepG2 cell and inhibition of hepatitis B virus and inhibition of the viral replicon were evaluated using dandelion and taraxasterol extracts after three and nine days of treatment. Outcomes showed that after three days of treatment, dandelion (100 μg/ml) and taraxasterol (6 μg/ml) showed maximum cell toxicity with cell viability less than 100% as compared to lamivudine. After nine days of treatment, dandelion (100 μg/ml) and taraxasterol (24 μg/ml) showed maximum cell toxicity as compared to lamivudine. Then inhibitions of hepatitis B virus infection, active hepatitis B virus, and hepatitis B virus deoxyribonucleic acid were evaluated with dandelion extracts (25 μg/ml, 50 μg/ml, and 100 μg/ml) and taraxasterol (1.5 μg/ml, 3.0 μg/ml, 6.0 μg/ml, 12 μg/ml, and 24 μg/ml) after three and nine days of treatment. Outcomes showed that dandelion (100 μg/ml) and taraxasterol (24 μg/ml) were observed with remarkable inhibition of hepatitis B virus infections. These data confirmed the importance of both dandelion and taraxasterol in the management of hepatitis B virus infections [36].

figure k

3.5 Plant Showing Anti-Influenza Virus Activity

He et al. stated the role of aqueous extract of dandelion against influenza virus. In this context, uxiaoganmaojiaonang and oseltamivir were considered as reference compounds. More than two hundred macro and micro species of dandelions exist in nature. Taraxacum officinale (TO) and Taraxacum erythrospermum (TE) are the most abundant species of dandelion. Taraxacum albidum (TA) and Taraxacum pamiricum (TP) are the most found species of dandelion in Japan. Taraxacum aphrogenes (TA), Taraxacum californicum (TC), Taraxacum centrasiaticum (TC), Taraxacum ceratophorum (TC), Taraxacum holmboei (TH), Taraxacum kok-saghyz (TK), Taraxacum laevigatum (TL), Taraxacum mirabile (TM), Taraxacum pankhurstianum (TP), Taraxacum platycarpum (TP) are other forms of dandelions, originated from Paphos, California, China, Colorado, Island, Russia, Northern part of north America, Turkey, Scotland, and Korea [24]. The principal components of dandelion are taraxacin, taraxacerin, taraxafolin, coumarin analogue, indole alkaloid, βcarboline alkaloid, choline (as vitamin B complex) along with vitamin A and C. Cell toxicity assay was performed using madindarbycanine kidney cells, which confirmed that dandelion (15 mg/ml) was observed with lowest viability rate less than 10%. Anti-viral activity against influenza virus was assessed using suxiaoganmaojiaonang (concentration: 4.375 mg/ml), dandelion (concentration: 2.5 mg/ml), and oseltamivir (concentration: 0.3 mg/ml). Results showed that dandelion was observed with maximum anti-influenza virus. Then influenza virus infected nucleoprotein ribonucleic acid levels were assessed using dandelion extract (2.5 mg/ml concentration) with respect to influenza virus infected human prototype isolate A/Puerto-Rico/8/34 cells. Then HEK293T (human embryonic kidney) cells with luciferase enzyme were used to evaluate luciferase activity using dandelion extract (2.5 mg/ml concentration) and oseltamivir (0.1 mg/ml concentration). Outcomes showed that dandelion was observed with maximum activity against the viral strain. These data confirmed that dandelion showed remarkable activity against influenza virus [37].

Dorra et al, experimentally proved the ethanolic extracts of Zingiber officinale (Ginger), Nigella sativa (Black seed), and Foeniculum vulgare (Fennel) in different concentrations 20 μg/ml, 40 μg/ml; 50 μg/ml, 100 μg/ml, and 150 μg/ml, 300 μg/ml active against influenza virus in terms of plaque forming unit with pretreatment viral load of 29 × 105 plaque forming unit in comparison with oseltamivir. Outcomes revealed that maximum activity was observed with 300 μg/ml of Foeniculum vulgare ethanolic extract with 82.8% viral inhibition with 5 × 105 plaque forming unit post viral load. These data confirmed the importance of fennel in the treatment of influenza [38].

Mehrbod et al. confirmed the role of garlic extract on influenza virus. In this context, cell toxicity assessment against madindarbycanine kidney cells using (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, inhibition of influenza virus load, presence of influenza virus in culture media (by Hemagglutination assay) on chicken red blood cell after one hour, eight hour and twenty- four-hour treatment were used to evaluate the anti-viral efficacies of garlic extract. Outcomes showed that 10 μg/ml of garlic extract was required to treat 50% population of influenza infected cells. Rest of the activities also confirmed that time exposure infection caused by influenza virus was markedly reduced. This information stated the anti-influenza activity of garlic extract [39].

3.6 Plant with Anti Coronavirus Activity

Thuy et al. confirmed the role of garlic extract in the management of coronavirus infection by in-silico way. The scientific name of garlic is Allium sativum belonging to Amaryllidaceae family. Gas chromatographic analysis of garlic confirmed the presence of eighteen essential oils such as diacetonalcohol (61), allyl sulfide (62), methyl allyl disulfide (63), 1,2-dithiole (64), allyl disulfide(65), allyl propenyl disulfide (66), allyl methyl trisulfide (67), 3-vinyl-1,2-dithiacyclohex-4-ene (68), 2-vinyl-4H-1,3-dithiine (69), carvone (70), allyl trisulfide (71), 2-propenyl propyl trisulfide (73), 1-propenyl-2-propenyl trisulfide (74), 1-propenyl methyl disulfide (75), diallyl tetrasulfide, and cyclic octaatomic sulfur. Among them, allyl disulfide was the primitive constituent with 28.44%. Then all the constituents were docked with 6 LU7 (crystal structure of coronavirus main protease enzyme) and angiotensin converting enzyme. Outcomes showed that allyl disulfide showed the maximum receptor interactions against 6 LU7 and angiotensin converting enzyme with(−)15.32 and(−) 12.84 dock score as well as root mean square deviations 1.35 and 1.46, respectively. These data stated the observable interactions between garlic and coronavirus infection [40].

figure l

Mosbauer et al. confirmed the satisfactory role of allicin (76) in the treatment of coronavirus infection. In this work, Vero E6 (kidney epithelial cell) and Calu-3 (lung cancer cell) cell lines were used to assess the anti-viral potential of allicin against coronavirus infections. Percent viable cells were estimated using allicin (0 μg/ml, 50 μg/ml, 75 μg/ml, 100 μg/ml, 150 μg/ml, 200 μg/ml, 250 μg/ml, and 300 μg/ml) and allicin (0 μg/ml, 50 μg/ml, 75 μg/ml, 100 μg/ml, and 150 μg/ml) against calu-3 and vero E6 cell lines, respectively. Results showed that viable cell counts were decreased with increased dose of allicin. In the assessment of post infection treatment with allicin, three groups were created such as allicin (50 μg/ml) pretreated coronavirus before infected the host, allicin (50 μg/ml) pretreated host cells before infected by virus, allicin (50 μg/ml) treated coronavirus infected host cells and assess their amount of infection causing particles and presence of coronavirus ribonucleic acid. Results showed that allicin significantly minimized the virus infection in host cell. To quantify the multiplicity of coronavirus infection in terms of amount of coronavirus ribonucleic acid and virus infected cells, calu-3 cells were treated with allicin (100 μg/ml and 200 μg/ml). Results showed that 200 μg/ml of allicin proved as a good agent to minimize coronavirus infections even after 16 h and 24 h of infection. As well as allicin (150 μg/ml) concentration showed remarkable decrease in coronavirus infection. Furthermore, it was confirmed that allicin fade away the level of interferon like gene related to host response and directed the cellular pathway toward normal calu-3 cell. These data confirmed the importance of allicin toward coronavirus infection [41].

figure m

Hoever et al. confirmed the role of licorice (Glycyrrhiza radix) in the treatment of coronavirus infection. Glycyrrhiza radix contained glycyrrhizin, 18 alpha glycyrrhetinic acid, and its different derivatives. In this context, vero cells were infected with coronavirus, then the effects of licorice active constituents and their derivatives on the infected cells were evaluated. Outcomes showed that compounds (77) and (78) were observed with good activity as effective concentration50 values were 5.0 micromolar and 8.0 micromolar, respectively. These data confirmed the role of licorice in the treatment of coronavirus infection [42].

figure n

3.7 Plant Against Viral Haemorrhagic Septicaemia Rhabdovirus

Micol et al. suggested that olive leaf extract and oleuropein (principal component of olive) showed its potency against haemorrhagic septicemia rhabdovirus. In this work, rhabdo septicemia virus infected epithelioma papulosumcyprini cells were used at 1011 foci forming unit value. Cell toxicity behavior of the leaf extract (concentrations: (0 μg/ml, 10 μg/ml, 20 μg/ml, 30 μg/ml, 40 μg/ml, 50 μg/ml, and 60 μg/ml) and oleuropein (concentrations: (0 μg/ml, 10 μg/ml, 20 μg/ml, 30 μg/ml, 40 μg/ml, 50 μg/ml, and 60 μg/ml) was assessed by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) 2H-tetrazolium] assay method. In the viral inhibitory effect of the substances, methylcellulose plaque formation assay method was used. Outcomes showed that both extract and oleuropein observed no cellular toxicity as well as after 3 days of treatment with olive leaf extract, level of viral infection was markedly reduced. This information stated the importance of olive extract in the growth of septicemia cause by rhabdovirus [43].

3.8 Plant Against Murine Norovirus

Gilling et al. suggested the role of oregano and its active constituent carvacrol (79) against murine norovirus infection. In the work, 4% oregano oil and 0.25%, 0.5% of carvacrol were used to evaluate the anti-viral effects against culture media infected with murine norovirus in a 0.25 h, 0.5 h, 1 h, 3 h, 6 h, and 24 h time line. Outcomes showed within 1 h of carvacrol treatment maximum inhibition against murine virus infection was observed [44].

figure o

3.9 Plant Extract with Anti-Respiratory Syncytial Viral Activity

Li et al. confirmed the importance of Mentha piperita leaves in the treatment of respiratory syncytial virus. In this work, ethanolic extract of Mentha piperita leaves (different concentrations: 5 μg/ml, 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml) was evaluated against respiratory virus as compared to ribavirin using Hep-2 cells. Mentha piperita leaves were extracted with absolute ethanol at 90°C for 2 h followed by washing with fractionated petroleum ether. After concentrating the volume of the extract, 4.27 gram of dried extract was obtained. Results showed that 50% inhibitory concentrations of extract and ribavirin were 10.41 μg/ml and 2.73 μg/ml, respectively. These data confirmed the importance of the plant in the treatment of respiratory syncytial viral infection [45].

3.10 Plant Species Used in the Treatment of Dengue Virus

Flores-Ocelot et al. developed anti-viral activities of methanolic extracts and dandelion (Taraxacum officinale) and stinging nettle (Urtica dioca) along with its different fractions (methanolic extracts of the plants fractionated by dichloromethane followed by eluting different concentration gradients of n-hexane and ethyl acetate) of both the plants against dengue viral strain (DENV2) at 60°C, 80°C, and 120°C temperatures. Outcomes revealed that maximum inhibition was observed with methanolic extracts of stinging nettle (60°C) and dandelion (85°C) with 50% inhibitory concentrations of 74.51 μg/ml and 179.1 μg/ml, respectively. These data confirmed the role of dandelion and stinging nettle in the treatment of dengue virus [46].

3.11 Anti-Viral Activities of Ocimum Basilicum

Chiang et al. confirmed the anti-viral activities of Ocimum basilicum (aqueous and ethanolic extracts) and its active constituents such as linalool, apigenin, and ursolic acid against herpes simplex virus (type 1 and 2 strains), adenovirus (type 3, 8, and 11 strains), hepatitis B virus (hepatitis B surface and e antigens) and enterovirus (coxsackievirus B1 and enterovirus 71) in comparison with acyclovir, 2′,3′-Dideoxycytidine, glycyrrhizin and lamivudine, ribavirin, respectively. Effective concentration (50%) of the extracts and molecules observed that ursolic acid and apigenin (80) showed remarkable inhibitions against all types of herpes simplex viruses with 6.6 mg/ml and 9.7 mg/ml concentrations; apigenin, ursolic acid, and linalool showed remarkable inhibitions against all types of adenoviruses with 11.1 mg/ml, 4.2 mg/ml, and 16.9 mg/ml concentrations; apigenin showed remarkable inhibitions against all types of hepatis B viruses with 7.1 mg/ml and 12.8 mg/ml concentrations and apigenin and ursolic acid showed remarkable inhibitions against all types of enteroviruses with 0.4 mg/ml and 0.5 mg/ml concentrations. These data confirmed the importance of basil plant in the management of different viruses [47].

figure p

All the chemical structures from 1-80 are inserted below.

4 Insight of the Book

Plant metabolites showed diversified anti-viral efficacies. This book will focus mainly on herpes simplex virus (type 1 and 2), hepatitis B virus, hepatitis C virus, pox virus, respiratory syncytial virus, gastrointestinal virus, influenza A virus, influenza B virus, polio virus, coronavirus, haemorrhagic septicaemia virus, vesicular stomatitis virus, adenovirus, cutaneous virus, dengue virus, neurological virus, encephalitis, virus causing cancer and genital warts, pogosta disease, coxsackie virus B3, cytomegalovirus B1, and Epstein-Barr Virus.

Stigmasterol, behenic acid, arachidic acid, gallic acid, eucalyptol, globulol, arjunin, arjunic acid, arjungenin, terminic acid, chebulinic acid, chebulic acid, ellagic acid, chebulagic acid, 1-deoxynojirimycin, moracin M and rutin are the most common plants metabolites active against herpes simplex virus. Lupeol, psoralen, hesperidin, azadirachtin, rutin, quercetin, and sitosterol are highly active plant metabolites active against hepatitis B virus. Epigallocatechin, silybin, oxymatrine, and matrine are the plant metabolites working against hepatitis C virus. Hydroxyisolonchocarpin, broussochalcone A, trihydroxyflavane, broussochalcone B, papyriflavonol A, kazinol A, kazinol B, kazinol F, kazinol J, broussoflavan A, andcryptoquindoline are the most active plant metabolites working against coronavirus. Phyllantin, astragalin metabolites are also effective against HSV, HBV, and HCV. Plumbagin, plumbagic acid, isoshinanolone are also effective against influenza virus. Salicylic acid, 4-hydroxy-3-methoxy-benzoic acid, gallic acid ethyl ester, 4-hydroxy-3,5-dimethoxy benzoic acid methyl ester, protocatechuic acid, gallic acid and catechin obtained from Ardisia chinensis showed activity against coxsackie virus B3. Eugenol, rosamaric acid, estragole, carvacrol, caryophyllene oxide from Ocimum sanctum observed with good anti-dengue virus activity.

5 Conclusions

In the chapter related to different medicinal plants along with its chemical constituents effective against various viral infections, total information is divided into nine categories such as plants effective against HIV, HSV, respiratory virus, HBV, rabies virus, influenza virus, coronavirus, rhabdovirus, and murine norovirus. Acacia catechu, olive, basil, Phyllanthus emblica, and Phyllanthus amarus showed marked effectivity against human immunodeficiency virus and acquired immune deficiency syndrome. Baccharis megapotamica, Ilex theezan, Glechonspathuluta, Camelia sinesis, Nerium oleander, lemon balm, Mallotuspeltatus, peppermint, Phyllanthus urinaria, Rhus aromatica, Rosmarinus officinalis, Salvia cedronella, Swertia chirata showed good activity against different strains of herpes simplex virus. Mentha piperita, Lafoensiapacari, Passiflora edulis, and Cyperus rotundus, Taraxacum officinale observed with good activity against viral strains associated with respiratory and hepatitis B, respectively. Allamandaschottii and dandelion, garlic, Salvia cedronella, fennel, black seed, ginger showed remarkable inhibitions of rabies and influenza viruses, respectively. Garlic, licorice, olive, and oregano are also effectively worked against coronavirus, septicemia causing rhabdovirus and murine norovirus, respectively. So, after detailed study about the role of medicinal plants and their metabolites in the treatment of viral manifestations we can say that natural products are the most beneficial treatment regime in this area along with its multiple positive sites such as minimal side effects, lesser toxicity, and interactions.