Introduction: Reported immunomodulatory activity of selected plants

The immunomodulating effects of Emblica officinalis were measured and documented using in-vitro and in-vivo models (Wang et al., 2019; Sai et al., 2002). Amla significantly inhibited chromium induced free radical production and restored the anti-oxidant status back to control level. It also inhibited apoptosis and DNA fragmentation induced by chromium (Jantan et al., 2019). Further, the fruit extract showed immunomodulatory activity via its antioxidant properties against arsenic induced oxidative stress and apoptosis in thymocytes of mice (Singh et al., 2013).

Shivaprasad et al., (2006) evaluated immunostimulant activity of Terminalia chebula extract on cell-mediated and humoral components of the immune system in mice. The result showed increase in humoral antibody (HA) titer and delayed-type hypersensitivity (DTH) in mice. In another study, Terminalia chebula extract (100 mg/kg/p.o.) was shown to increase the level of liver mitochondrial enzymes CAT and SO) as well as GSH along with decrease in the level of lipid peroxidation in the liver when compared to the vehicle, sheep red blood cells (SRBC) and cyclophosphamide-treated groups suggesting immunostimulating effects of the extract (Aher et al., 2011).

Berberis Aristata, revered medicinal plant, showed immunomodulating effects via shifting cell immune response to Th2, T reg induction, inhibition of inflammatory cytokines (IL-1, TNF, and IFN-γ), and stimulation of IL-4 and IL-10 determined in-vitro and in-vivo (Kalmarzi et al., 2019; Kumar et al., 2016).

The aqueous extract of Solanum xanthocarpum, commonly called as Kantkari, showed immunomodulating properties via reducing oxidative stress and inflammatory biomarkers in ovalbumin induced immunized rats (experimental model of asthma) (Gulati et al., 2016). βsitosterol & stigmasterol were reported to be responsible from immunomodulating effects of Kantkari (Khanam et al., 2012).

The crude extract of Curcuma zedoaria when administered intraperitoneally showed a significant increase in total white and red blood cell counts, a decrease in peritoneal cell number and tumor volume reduction, whereas the oral administration revealed a noteworthy augmentation only in total leukocyte count. These results are of suggestive that it has immunomodulating effects (Carvalho et al., 2010).

Gingiber officinalis, commonly known as Sunthi, is well documented for its effects on immune system demonstrated by various in-vitro and in-vivo assays (Talpurabd et al., 2013; Carrasco et al., 2009; Wilasrusmee et al., 2004; Tan et al., 2004). [6]-gingerol has been documented as an immunomodulating compound from Gingiber officinalis (Amri et al., 2016).

Mallurwar et al., (2008) evaluated Ficus Religiosa extract for its immunomodulatory effects in mice. Administration of extract remarkably ameliorated both cellular and humoral antibody response. In another study, root (0.5 mg/ml) and leaf extracts (30 mg/ml) of the plant was found to have anti-inflammatory and thus, immunomodulatory activity (Gupta et al., 2014).

A polysaccharide isolated from Marshdenia Tenacissima caused increase in the serum hemolysin, promoted the formation of antibody-forming cells, improved the phagocytosis of mononuclear macrophage in normal mice and reduced the growth of H22 tumour in mice by combating oxidative stress and elevating serum inflammatory markers. These results suggest that isolated polysaccharide could regulate the immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice (Wang et al., 2018; Jiang et al., 2016).

Tinospora Cordifolia has been reported to have great influence of immune system (Alsuhaibani et al., 2017; Kalikar et al., 2008; Aher et al., 2010; Sharma et al., 2012).In immunocompromised rats (cyclophosphamide induced), the treatment with leaf extract for 15 days increased humoral antibody production (Aasiya et al., 2016). The extract was also reported to enhance macrophage activation in J774A cell lines (More et al., 2011). Sharma et al., (2012) reported 11-hydroxymustakone (2), N-methyl-2-pyrrolidone (3), Nformylannonain (1), cordifolioside A (4), magnoflorine (5), tinocordiside (6), syringing as immunomodulators from Tinospora Cordifolia.

Alhagi Maurorum extract inhibited the proliferation of Jurkat cells in a dose-dependent manner at concentrations higher than 31.25 μg/mL (IC50 44.81μg/ml) indicating its immunomodulatory properties (Hamedi et al., 2015).

Picrorhiza kurrooa (Kutaki) is widely explored for its immunomodulatory effects. Comparative study between alcoholic and aqueous extracts showed that the alcoholic extract had higher potent effects in enhancing the humoral and cellular immunity against mouse model of cyclophosphamide-induced immunosuppression (Hussain et al., 2013). Another study revealed that the alcoholic extract exhibited no mitogenic activity but augmented the responsiveness of murine splenocytes to T cell mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and B cell mitogen lipopolysaccharide (LPS E. colt) and suggested these properties as mechanism behind its immunostimulating action (Sharma et al., 1994).

Fumaria Officinalis, on concurrent daily administration for 7 days, reversed ethanol induced decrease in the humoral and cell-mediated immune response, phagocytosis, phagocytosis index, total leukocyte count, reduced glutathione, catalase and superoxide dismutase activities and increase in lipid peroxidation (Wasu et al., 2009). 

Cyperus scariosus ethanolic extract on oral administration inhibited both humoral and cellmediated immune responses by suppressing primary (26.8 %) and secondary (29.7 %) antibody titres, and also inhibited cell-mediated delayed type hypersensitivity (DTH) immune response (45.9 %) at 600 mg/kg dose, phagocytosis – both in vitro (37.4 %) and ex vivo (37.8 %) – and delayed the graft rejection time (45.8%), suggesting immunomodulatory effects (Bhagwat et al., 2009).

Mubashir et al., (2014, 2017) scientifically revealed the role of Gentian kurroo, a traditionally used drug for enhancing immunity, in treating immune disorder like arthiritis. The author reported the immunosuppressive effects (both cellular and humoral) of the methanolic extact as a consequence of its ability to reduce inflammation and B and T cell proliferation in splenocyte in rats.A mild immunostimulatory effect of Cida cordifolia was recorded by Ouédraogo et al., (2012) in immunosuppressed wistar rats.

Different parts of Azadirachta indica are indicated for their effects on immune system (Rather et al., 2017). Pretreatment of mice with neem oil showed enhanced phagocytic activity and expression of MHC class-II antigens, higher lymphocyte proliferation in spleen. The results indicated the non-specific immunostimulatory properties of neem oil (Upadhyay et al., 1992). The flowed extract exhibited increased production of super oxide and nitric oxide in murine peritoneal macrophages along with significant increase in phagocytic index, activation of reticuloendothelial system through release of the mediators, antibody titer against the ovalbumin and protection towards the cyclophosphamide induced myelosuppression in dose dependent manner (Abhishek et al., 2009).

The root extract of Inula racemosa prevented compound 48/80 induced mast cell degranulation (Choudhary et al., 2012). The fructan fraction isolated from the extract increased delayed type hypersensitivity response, % neutrophil adhesion and in vivo phagocytosis in animals (Mishra et al., 2016).

Glycrrhiza glabra polysaccharide significantly suppressed tumor growth and increased immune organ index evident by activation of CD4+ and CD8+ immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels in mice (Ayeka et al., 2017). When liquorice aqueous extract (1.5 g/kg) was administered with zinc, an increase in leukocyte count, phagocytic index, HA titre and antibody secreting cells of mouse spleen was reported (Mazumder et al., 2012). These results showed immunomodulatory potential of mulethi (Abtahi Froushani et al., 2014).

Trachyspermum ammi (500 mg/kg, 14 days) showed immunostimulant activity in delayedtype hypersensitivity assay. A glycoprotein isolated from ajowan at 1 μg/mL induced proliferation of B-cell enriched murine splenocytes and activated macrophages in releasing NO and promoted phagocytosis (Shruthi et al., 2017).

In-vitro and in-vivo studies showed immunomodulatory potential of Clerodendrum serratum aqueous root extract. Macrophages treated with extract exhibited increased acid phosphatase and myeloperoxidase activity as well as significant increase in the production of nitric oxide and hydrogen peroxide. Administration of extract at doses of 100 and 200mg/kg p.o. significantly increased in total leukocyte count and in weight of spleen indicating an uplift of innate immunity in mice (Juvekar et al., 2006).

Badole et al., (2019) valuated the immunomodulatory activities of Putranjiva roxburghii by studying their protective effects against leucopenia/ neutropenia produced by a single dose of cyclophosphamide on Swiss albino mice. The extract prevented leucopenia and neutropenia produced by cyclophosphamide in mice and showed immunostimatory effects.

Alum is commonly used as an adjuvant in developing vaccine targeting immunity (Oleszycka et al., 2014; Pandit et al., 2007). It augmented the action of developed vaccines (Moschos et al., 2006; Matthew et al., 2019)

The effect of Swertia chirata on humoral and cell mediated immunity responses was determined in mice by estimating T lymphocytes (CD3 and CD19) and Th1 cytokines (IL-2, IFN-γ and IL-4) in mouse model of cyclophosphamide induced immunosuppression. The extract showed dose related decrease in primary and secondary antibody response and delayed type hypersensitivity response with the maximum decrease at 200 mg/kg (Ahirwal et al., 2013).

The volatile oil of Cedrus deodara wood, administered orally at doses of 50 and 100 mg/kg, significantly inhibited neutrophil adhesion to nylon fibers, indicating inhibition of process of margination in the blood vessels. It also significantly inhibited Type III hypersensitivity reaction, i.e. Arthus reaction induced by methylated bovine serum albumin, and Type IV, i.e. delayed type hypersensitivity reaction induced by sheep erythrocytes and oxazolone, indicating an inhibitory effect on humoral and cell-mediated immune responses (Shinde et al., 1999; Narayan et al., 2017).

The oral administration of aqueous extract of the Tricosanthes Dioica Roxb to mice showed increased antibody production in dose dependent manner along with enhanced production of RBC, WBC and haemoglobin (Singh et al., 2012). 

Andrgraphis paniculata in combination with Tinospora cordifolia showed a significant increase in macrophase count, neutrophil adhesion, haemagglutinating antibody titre and delayed type hypersensitivity (DTH) response. In rats immunized with sheep RBC, it potentiated the cellular immunity (Yadav et al., 2016). Andrographis paniculta extract in chicken showed strong antibody titer and significantly higher skin thickness indicating potent immunomodulatory activity (Nety et al., 2018). Further, andrographolide treatment in vitro attenuated both LPS and IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). It also down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages (Wang et al., 2010).

Pongamia glabra seed and bark extract were studied against cyclophosphamide induced immunosuppression in mice. Both the extracts showed dose dependent counteracting effect to that of reduction in RBC counts, Hb% and DLC (Heroor et al., 2012). The immunomodulator activity was also studied by Shinde et al., (2011) by using carbon clearance test,eEffect on serum immunoglobulins and cyclophosphamide induced neutropenia. In these entire paradigms 400 mg/kg dose was reported to have more significant result than its 200 mg/kg of dose.

Syzigium aromaticum essential oil increased the total white blood cell (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in mice. Moreover, it restored cellular and humoral immune responses in cyclophosphamide-immunosuppressed mice in a dose-dependent manner (Carrasco et al., 2009). The leaf extract increased the proliferation activity at dose of 15, 75, and 150 mg/kg, increased lymphocytes at dose 150 mg/kg, increased the activity of macrophage ROI secretion at dose of 150 mg/kg, and increased in lymphoblast in mice infected with Salmonella typhimurium (Dibazar et al., 2015; Wael et al., 2018).

The immunomodulatory activity of rhizome and seed extracts of Nelumbo nucifera was evaluated by Mukherjee et al., (2010), using various in vivo models including the total and differential leukocyte count (TLC and DLC), nitroblue-tetrazolium reduction (NBT) test, neutrophil adhesion test, phagocytic response and delayed type hypersensitivity (DTH) reaction. Sheep red blood cells (SRBC, 5 x 10(9)cells/ml) were used to immunize the animals. A dose-dependent potentiation of DTH reaction induced by SRBC was reported for both the extracts. The animal studies showed that hot water-soluble polysaccharides from lotus seeds inhibited tumor growth in H22 tumor-bearing mice by improving the immune response by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2 (Zheng et al., 2016).

Hexane fraction of Cinnamomum tamala inhibited the delayed type of hypersensitivity response antibody production, suppressed mitotic index in bone marrow cells along with the suppression of lymphocyte proliferation against concanavalin A mediated proliferation of lymphocytes in rats (Chaurasia et al., 2010). On 30 days treatment, the same fraction (800 mg/kg) significantly suppressed growth rate, increase of spleen and thymus weight and low bone marrow cellularity.

Myristica fragrans lignans possessed immunomodulatory activity in mammalian splenocyte by inhibiting the proliferation of splenocytes, transcription of IL-2 and IL-4 genes in response to polyclonal T cell mitogen concanavalin A. The production of IL-2, IL-4 and IFN-gamma cytokines was also significantly inhibited (Checker et al., 2008).

Aconitum heterophyllum was reported to stimulate phagocytic function while inhibiting the humoral component of the immune system (Atal et al., 1986).

Curcuma longa is an Ayurveric medicinal plant recommended for general well being. It is reported to possess marked immunomodulatory effects determined using numerous invitro models (Funmilayo et al., 2018; Alambra et al., 2012; Gautam et al., 2007).

Nanoparticulate curcumin, bioactive component from Curcuma longa, stimulated higher early cell-mediated immune response at 5 mg/kg and 10 mg/kg in mice sensitized with sheep red blood cells (Afolayan et al., 2018). Curcumin is also documented to inhibit cell proliferation and cytokine production by inhibiting NF-κB target genes in mouse macrophage cells (Yadav et al., 2005). Treatment of NR-INF-02 showed a significant increase of NO, IL-2, IL-6, IL-10, IL-12, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and MCP-1 production in unstimulated mouse splenocytes and mouse macrophages. It also showed potent inhibitory effect towards release of PGE 2 and IL-12 levels in LPS stimulated mouse splenocytes (Chandrasekaran et al., 2013).

Different doses of aqueous root extract of Santalum album (0.5-30 mg/ml, 50 µl) inhibited proliferation, nitric oxide production and CD14 monocyte surface marker exhibiting immunopharmacological properties (Gupta et al., 2016).

Administration of Sida cordifolia showed immunostimulating effects in immunosuppressed broilers (cyclophosphamide induced) (Tekade et al., 2008). A formulation containing Sida cordifolia on oral administration to rats showed a significant increase in neutrophil adhesion and delayed type hypersensitivity response whereas the humoral response to sheep RBCs was unaffected (Fulzele et al., 2003).

Aminoglucosyl glycerolipid isolated from Desmodium gangeticum enhanced nitric oxide (NO) production and provided resistance against infection established in peritoneal macrophages by the protozoan parasite Leishmania donovani (Mishra et al., 2005)

The different doses of Strychnos nux vomica extract were found to significantly suppress the induction of ovalbumin-specific IgE antibody response in mice confirming its immunosuppressive activity (Duddukuri et al., 2008).

1.2: Introduction: Reported Antiviral activity of selected plants 

It has been shown that polyphenols isolated from E. officinalis exerted significant inhibition on herpes virus. Anti-herpes activity of 1,2,4,6-tetra-O–d-glucose, isolated from E. officinalis, was deliberated and HSV-1E and HSV-1L gene expression was found to be inhibited leading to inactivation of extracellular viral particles and inhibition of viral biosynthesis in host cells (Xiang et al., 2011).

Lin et al the extract of fruits of Terminalia chebula showed inhibitory effects on human immunodeficiency virus-1 reverse transcriptase. Hot water extract of Terminalia chebula showed anti-herpes simplex virus (HSV) activity in-vivo and anti-cytomegalovirus (CMV) activity both in-vitro and in vivo in a study. Terminalia chebula inhibited HSV-1 entry at non-cytotoxic doses in A549 human lung cells by preventing binding, penetration, and cell to cell spread, as well as secondary infection.

The roots of Berberis aristata DC. (Berberidaceae) are used in the traditional medicine for malaria in various parts of India. Aqueous root extract showed in vitro antiplasmodial activity with an IC50 value of 40 µg/mL

Alcoholic extract of Solanum xanthocarpum exhibited HIV Reverse Transcriptase enzyme. The fruit extract of S. xanthocarpum is reported to cause high mortality rate against the mosquito larvae (Kumar et al., 2012).

In vitro results showed that compound of Curcuma zedoaria volatile oil was effective in the treatment of H5N1 via the mechanisms including virus killing, virus inhibiting, the prevention of the virus spread, and the treatment of the virus-related injury in MDCK (Huang et al., 2009).

A lyophilized juice extract from Zingiber officinale at different concentrations (5, 25, 50, 75, 100, 150 and 200µg/ml) were tested in vitro as anti- hepatitis C virus (HCV) using the hepatocellular carcinoma HepG2 cell line infected with HCV. The extract was reported to inhibition viral replication inside the HCV-infected HepG2 cells (El-Wahab et al., 2009). The sequiterpenes present in Zingiber officinale was found to have antirhinoviral activity (Denyer et al., 1994).

Piperamides isolated from a combined methanol/dichloromethane extract of Piper nigum were tested for antiviral properties against three viruses related to upper respiratory tract infections. Compounds were effective only against coxsackie virus type B3 (CVB3) with an IC50 of 10.6 µg/mL in a cytopathic effect inhibition assay and it showed no activity against further two investigated viruses, i.e. human rhinovirus type 2 (HRV2), and influenza virus type A (HK68) (Mair et al., 2016).

The antiviral activity of Ficus religiosa was investigated against RSV and HRV in vitro by plaque reduction and virus yield assays, and the major mechanism of action was investigated by virus inactivation and time – of – addition assays. Ficus religiosa methanol bark extract was most active against HRV with an EC50 of 5.52 µg/ml. This extract inhibited late steps of replicative cycle. Water bark extract was the most active against RSV with an EC50 between 2.23 and 4.37 µg/ml. Partial virus inactivation and interference with virus attachment were both found to contribute to the anti-RSV activity. Replication of both viruses was inhibited in viral yield reduction assays (Cagno et al., 2015).

The anti-HIV activity of marstenacissides isolated from Marshdenia tenacissima was evaluated against HIV-1-infected SupT1 cells in vitro (Pang et al., 2016, 2017). The activity test showed that all 56 compounds at the concentration of 30 μM displayed minor or negligible effects against SupT1 cells (HIV-1 inhibition rate from 8.26% to 81.3%), and the C21 steroid and C21 steroidal diglycoside displayed relatively stronger activities than the C21 steroidal triglycoside and C21 steroidal tetrglycoside.

Tinospora cordifolia extract has been shown to demonstrate a decrease in the recurrent resistance of HIV virus thus improving the therapeutic outcome (Kalikar et al., 2008). AntiHIV effects of TCE was revealed by reduction in eosinophil count, stimulation of B lymphocytes, macrophages and polymorphonuclear leucocytes and hemoglobin percentage thus, revealing its promising role of application in management of the disease (Akhtar, 2010).

The 80% methanolic extract of Alhagi maurorum is reported to inhibit foot and mouth disease causing viruses. The extract is reported to inhibit virus replication (ElhamRezatofighi et al., 2016).

In comparison to 34 Saudi Arabian medicinal plants, Picrorhiza kurroa extract showed appreciable inhibition of anti-hepatitis B virus in HepG2.2.15 cells (Arbab et al., 2017).

Results showed that neem bark (NBE) extract significantly blocked HSV-1 entry into cells at concentrations ranging from 50 to 100 μg/mL (Yerima et al., 2012). Furthermore, blocking activity of NBE was noticed when the extract was preincubated with the virus but not with the target cells suggesting a direct anti-HSV-1 property of the neem bark (Tiwari  et al., 2010).

Leaves extract of neem (Azadirachta indica A. Juss.) (NCL-11) has shown virucidal activity against coxsackievirus virus B-4 as suggested via virus inactivation and yield reduction assay besides interfering at an early event of its replication cycle (Badam et al., 1999).

The antiviral activity of Glycrrhiza glabra extracts against different viruses has been reported, including herpes simplex, Varicella zoster, Japanese encephalitis, influenza, and vesicular stomatitis virus (Wang et al., 2015). Different studies have demonstrated that two triterpenoids are responsible for the antiviral activity reported: glycyrrhizin and 18β glycyrrhetinic acid (Wang et al., 2015). These compounds have the ability to inhibit virus gene expression and replication, decreasing the adhesion force and stress and reducing HMGB1 binding to DNA (Hattori et al., 1989; Wang et al., 2015). Also, they can enhance host cell activities by blocking the degradation of IκB enzyme involved in the propagation of the cellular response to inflammation, activating T lymphocyte proliferation, and suppressing host cell apoptosis (Wang et al., 2015).

The in vitro antiplasmodial activity of HA whole plant extracts (chloroform and petroleum ether) using parasite lactate dehydrogenase (LDH) assay was studied. The extracts significantly reduced parasitemia in Plasmodium berghei-infected mice as compared to chloroquine with ED50 value at 18.29 mg/kg BW where the chloroform extract showed a significant activity with IC50 value at 16 μg/ml. The cytotoxic effect on rat skeletal muscle myoblast cells (L6 cells) was studied, and no cytotoxicity was observed up to 16 μg/ml (Verma et al., 2011).

The antiviral activity of Trachyspermum ammiessential oil was evaluated against Japanese encephalitis virus by the plaque reduction neutralization test. 80% virus inhibition by 0.5mg/ml of ajwain oil was reported (Roy et al., 2015).

The in-vitro assay was used to test the anti-viral activity of Swertia chirata against Herpes simplex virus type-1. Swertia plant crude extract (1 gm/mL) at 1:64 dilution inhibited HSV1, plaque formation at more than 70% level (Verma et al., 2008).

Crude aqueous extract of the Pongamia glabra seed completely inhibited the growth of herpes simplex virus type-1 (HSV-1) and HSV-2 at concentration of 1 and 20 mg/ml (w/v), respectively, as shown by complete absence of cytophatic effect (Elanchezhiyan et al., 1993). Crude decoction of dried leaves had no activity against rotavirus (Brijesh et al., 2006). However, oral administration of ethanolic extract of the leaves (200 and 300 g extract/g of body weight of shrimp/day) inhibited the growth of White Spot Syndrome Virus (WSSV) and increased the survival rate for the WSSV-infected shrimp to 40% and 80%, respectively (Rameshthangam and Ramasamy, 2007).

The antiviral activity of eugeniin, a compound isolated from S. aromaticum and from Geum japonicum, was tested against herpes virus strains being effective at 5 µg/mL, and it was deducted that one of the major targets of eugeniin is the viral DNA synthesis by the inhibition of the viral DNA polymerase (Kurokawa et al., 1998). In another study, aqueous extracts of S. aromaticum (L.) Merr. et Perry showed strong antiherpes simplex virus type 1 (HSV-1) activity when combined with acyclovir. This synergic activity was stronger in the brain that in the skin and it was also proved that those combinations were not toxic to mice (Kurokawa et al., 1995).

Kuo et al., 2005, reported the antiviral activity of Nelumbo nucifera seed ethyl alcohol extract on herpes simplex type 1 (HSV-1). At a dose of 100 g/mL, ethyl alcohol extract of lotus markedly inhibited HSV-1 replication with IC50 of 50.0 g/mL for replication. Various subfractions of Nelumbo nucifera seeds butanol (NNB) extract were investigated for the HSV-1 inhibitory effects indicating that NN-B-5 out of major nine fractions, NN-B1 to NNB-9, had the highest suppresser activity (Kuo et al., 2005).

Water extract of Curcuma longa decreased the number of local necrotic lesions on infected leaves of Nicotiana glutinosa by 68% compared with untreated controls. Curcumin and its derivative containing boron inhibited the HIV 1 protease (Yuchi et al., 1997). Curcumin used at the concentration of 10 to 100 nmol inhibited Tat transcription of HIV I-Itr Lac Z by 7080% in HeLa cell models (Barthelemy et al., 1998). Curcumin is also known to inhibit DNA polyrnerase, HIV and avian myeloblastosis virus reverse transoriptase (1).

The antiviral properties of Vetiveria zizanioides were reported against against dengue virus using docking analysis. The compound Ethyl 4-(4-methylphenyl)-4-pentenoate was found to have effective antiviral property (Lavanya et al., 2016).

Sandalwood oil, the essential oil of Santalum album L., was tested for in vitro antiviral activity against Herpes simplex viruses-1 and -2. It was found that the replication of these viruses was inhibited in the presence of the oil. This effect was dose-dependent and more pronounced against HSV-1 (Benencia et al., 1999).

From the whole plant of Sida cordifolia, the compound (10E, 12Z)-9-hydroxyoctadeca10,12- dienoic acid (20, Fig. 4) was isolated. This hydroxyl unsaturated fatty acid was found to be an exceptional NES (nuclear export signal) nonantagonistic inhibitor for nuclear export of Rev. Replication of HIV-1 is essentially dependent on the regulatory protein Rev or the Rev protein. The latter is involved in the nucleus-cytoplasm export of mRNA, which is in turn responsible for synthesis of the viral proteins necessary for viral replication. Several analogs of 20 were synthesized and tested for nuclear export of Rev inhibitory activity, but the parent compound proved to be the most potent. Previously, compound 20 was recognized as a natural anti-HIV agent (Tamura et al., 2010).