key: cord-1017624-gm688161
authors: Mukhtar, Muhammad; Arshad, Mohammad; Ahmad, Mahmood; Pomerantz, Roger J.; Wigdahl, Brian; Parveen, Zahida
title: Antiviral potentials of medicinal plants
date: 2007-11-05
journal: Virus Res
DOI: 10.1016/j.virusres.2007.09.008
sha: eb6c9a9d047ada19444c5dfc2920ba700db5a737
doc_id: 1017624
cord_uid: gm688161

Medicinal plants have been widely used to treat a variety of infectious and non-infectious ailments. According to one estimate, 25% of the commonly used medicines contain compounds isolated from plants. Several plants could offer a rich reserve for drug discovery of infectious diseases, particularly in an era when the latest separation techniques are available on one hand, and the human population is challenged by a number of emerging infectious diseases on the other hand. Among several other ailments, viral infections, particularly infections associated with human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2), and newly emerging infectious viruses have challenged mankind survival. Of importance, a variety of medicinal plants have shown promise to treat a number of viral infections, and some of them possess broad-spectrum antiviral activity. In the past, exploration into the antiviral activity of various promising medicinal plants was limited due to: (a) highly infectious nature of viruses and (b) lack of appropriate separation techniques for the identification of antiviral components from plants. Development of vector-based strategies, in which non-infectious molecular clone of a virus could be used for antiviral screening purposes, and advancement in separation technologies offers promise for medicinal plants usage in modern drug discovery. This article describes potential antiviral properties of medicinal plants against a diverse group of viruses, and suggests screening the potential of plants possessing broad-spectrum antiviral effects against emerging viral infections.

The history of medicinal plants dates back to the origin of human civilization on earth. Several of these may have been used to treat viral infections in the past, however, first recognized interest in their development as antiviral agent is the efforts of the Boots drug company (Nottingham, England) to screen 288 plants for anti-influenza activity (Chantrill et al., 1952) . Later studies have reported the inhibitory effects of medicinal plants extracts on the replication of several viruses. Particularly herpes simplex virus type 2 (HSV-2) (Debiaggi et al., 1988) , HIV (Asres and Bucar, 2005; Vermani and Garg, 2002) , hepatitis B virus (HBV) Kwon et al., 2005) , and emerging viral infections associated with poxvirus and severe acute respiratory syndrome (SARS) virus (Kotwal et al., 2005) were strongly inhibited by various plants extracts. Most of these studies have utilized either water soluble or alcoholic extracts of medicinal plants, and limited efforts have been directed toward the identification of active natural ingredient exhibiting antiviral effects. Moreover, recent studies showing antiviral potential of plant extracts against viral strains resistant to conventional antiviral agents (Serkedjieva, 2003; Tolo et al., 2006) have challenged the modern drug discovery practices, and deem a very careful look toward exploring natural antiviral components of medicinal plants.

The molecular mechanisms associated with the antiviral effects of plant extracts may vary among different viruses. However, the potentials of plant extract to boost inherent antiviral defense of human body which involves an intricate immune system might utilize common pathways. In recent past, a number of studies have explored immunostimulatory properties of plant extracts having antiviral properties (Webster et al., 2006) . The root extracts of medicinal plant Heracleum maximum Bartr. (Umbelliferae) which possess antiviral effects besides antifungal and antibacterial properties, stimulated Interleukin 6 (IL-6) production in the macrophage activation assay, confirming antiviral effects association with the immunostimulatory properties (Webster et al., 2006) . Furthermore, Plantago major Linn. and P. asiatica Linn. (Plantaginaceae) commonly used plants as folk medicine in Taiwan for the treatment of infectious diseases, exhibited lymphocyte proliferation and secretion of interferon-gamma (IFN-␥) at low concentrations. Both lymphocyte proliferation activity and induced secretion of interferon-gamma (IFN-␥) are indicators of cell-mediated immune response modulation (Chiang et al., 2003) . Along with similar lines, Sambucol, a product isolated from Sambucus nigra L., which is effective against various strains of influenza had shown to boost immune responses by secreting inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, and IL-8) (Barak et al., 2001) .

Besides immunomodulatory effect, another intriguing finding is the broad-spectrum antiviral nature of plant extracts (Pompei et al., 1979) . This could be associated with a single phytochemical, or a number of different plant constituents. Among several such observations few are: (i) an extract of the Trifollium species Secomet-V exhibited antiviral effect against a number of infectious viruses such as human papillomavirus, Marburg, influenza, HIV, HBV and HCV (Kotwal et al., 2005) , (ii) Pandanin, a lectin isolated from the saline extract of the leaves of Pandanus amaryllifolius Roxb. showed antiviral effect against HSV-1 and influenza virus strain H1N1 (Ooi et al., 2004) , (iii) crude extract of hop showed antiviral effect against a diverse group of viruses, suggesting the presence of broadspectrum antiviral phytochemicals in various parts of the plants (Buckwold et al., 2004) .

Medicinal plants have been used throughout the world, however, their wide usage had been limited to China, India, Japan, Pakistan, Sri Lanka, Thailand and a number of African countries. A detailed review has previously described national activities around the globe relevant to medicinal plants usage priorities (Hoareau and DaSilva, 1999) . Developed countries are also turning to encourage the usage of plant-based natural medicinal product in their healthcare systems. The Natural Health Product Regulations of Canada promulgated in January 2004 is an important step toward modernization of plant-based product usage in healthcare. This regulation encourages usage of modern technology and evidence-based scientific support toward promoting medicinal plants and the associated products (Siow et al., 2005) (Table 1 ). Tolo et al. (2006) Phyllanthus urinaria L. 1346TOGDG and geraniin isolated from Phyllanthus urinaria inhibited HSV-1 and HSV-2, respectively Yang et al. (2007) Influenza virus Geranium sanguineum L. A medicinal plant reducing the infectivity of various influenza virus strains in vitro and in vivo (Pantev et al. (2006) and Serkedjieva (1997) 

A randomized, double-blinded placebo-controlled study revealed that elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza 

The aqueous extract of neem leaves inhibited DEN-2 both in vitro and in vivo Parida et al. (2002) are anecdotal and lack scientific validity. Moreover, there is lack of qualified personnel in the field of medicinal plants. Appropriate clinical trials are also necessary for validating medicinal usage of plants among humans. The CATIE's "Practical Guide to Herbal Therapies for People Living with HIV" is a good start highlighting the potentials of phytochemicals extracted from plants. Further exploration and identification of natural products for controlling HIV and associated infections is necessary due to several reasons. First, efforts in the past to find an effective cure for HIV infection has met with disappointing results. Second, development of vaccine for HIV pandemic seems a far-fetched dream. The most effective therapeutic regimen for HIV-infected individuals is highly active antiretroviral therapy (HAART) which is a combination of protease inhibitors and nucleoside or non-nucleoside reverse transcriptase inhibitors. HAART can only control HIV infection among individuals continuously on therapeutic regimen and withdrawal of medication leads to reemergence of the diseases. Furthermore, based on HIV pathogenesis efforts have been made to target every step of viral life cycle starting from entry to viral morphogenesis as shown in Fig. 1 , however, none of these strategies have led to cure.

The plant kingdom is highly diverse and ranges from unicellular microscopic plants to long-lived huge trees. Screening of each and every plant or their individual parts (stem, leaves, roots, flowers, bark) for the identification of antiviral components is impossible. Current knowledge relevant to antiviral properties of medicinal plants is based on subjective information. There are also examples of antiviral properties of plants, or phytochemically screened products based on the properties of newly identified phytocomponents. One such example is a potential antiviral compound, cyanovirin N (CV-N), an 11-kDa protein isolated from the cyanobacterium Nostoc ellipsosporum. The CV-N possesses broad-spectrum antiviral activity besides inhibiting HIV-1 infection (Boyd et al., 1997) and is on the list of potentially emerging antiviral compounds (De Clercq, 2005; Witvrouw et al., 2005) . The antiviral activity of CV-N has been dissected at molecular levels and involves highly specific interactions with the viral envelope glycoprotein gp120 (Barrientos et al., 2003; Esser et al., 1999) . The viral envelope plays a major role in the infectivity of permissive cells and mediates interactions with permissive cells CD4 receptors in concert with chemokine receptors, CXCR4, CCR5. There is also a class of antiviral compounds known as HIV entry inhibitors, which (Fu et al., 2006; Kostova, 2006; Woradulayapinij et al., 2005) .

Medicinal plants have also shown inhibitory effects on viral protease (PR), an enzyme essential for proteolytic processing of polyprotein precursor into proteins essential for the assembly of viral particles. Of importance, HAART, the most favorable therapeutic regimen for treating HIV-infected individuals also contain protease inhibitors as part of the combination drugs cocktail. In the past, phytochemicals, such as triterpene derivatives from a number of medicinal plants have shown inhibitory effects on PR (Huang and Chen, 2002; Hussein et al., 1999; Park et al., 2005; Yu et al., 2005 Yu et al., , 2006 . Ongoing efforts are crucial toward further development of previously characterized protease inhibitors and identification of new compounds with such activity. Naturally occurring RT and protease inhibitors in various medicinal plants also offer a reserve of unexplored antiviral compounds.

Several members of the human herpesviruses (HHV) family are causative agent for human diseases. The majority of HHV infections are associated with HSV-1 and HSV-2. The other members of herpesviruses causing different illnesses are: HHV-3 (varicella zoster virus), HHV-4 (Epstein Barr virus), HHV-5 (Cytomegalovirus), HHV-6, HHV-7 and HHV-8.

In the past, most of the medicinal plants have been explored against a single member of herpes family, i.e. HSV. For example, aqueous extract of plant material has been used to treat HSVassociated infections. The phytochemical, Podophyllotoxin, isolated from the aqueous extract of Podophyllum peltatum L. inhibited HSV type 1 (HSV-1) (Bedows and Hatfield, 1982) . Besides aqueous extracts, organic solvents extracts of various plants have also shown anti-HSV activity, suggesting varied nature of antivirals present in medicinal plants. Two compounds namely geraniin and 1,3,4,6-tetra-O-galloyl-betad-glucose (1346TOGDG), isolated from the acetone extract of another plant Phyllanthus urinaria, also suppressed HSV-2 and HSV-1 (Yang et al., 2007) . HSV infections are usually serious problems among immunocompromised individuals, particularly HIV-infected individuals. Moreover, development of resistant herpes strains refractory to conventional antiviral drugs is also a major issue. There has always been a quest for antiviral which can overcome resistant strains of viruses or suppress emergence of viral resistance. Based on available information one can easily speculate about the presence of natural antiviral compounds effective against resistant strains of viruses. One such precedent is an aqueous extract from the roots of Carissa edulis (Forssk.) Vahl (Apocynaceae), a medicinal plant locally growing in Kenya, showing remarkable anti-HSV activity in vitro and in vivo for both wild type and resistant strains of HSV (Tolo et al., 2006) .

The quest for influenza virus natural inhibitors is very ancient. In the past century, several scientific efforts have been directed toward identifying phytochemicals capable of inhibiting influenza virus (Cochran et al., 1966; May and Willuhn, 1978) . Studies in the past and recent literature suggest that a variety of natural products isolated from several plants inhibit influenza virus both in vitro (Mothana et al., 2006; Pantev et al., 2006; Prajoubklang et al., 2005) and in vivo (Ivanova et al., 2005; Prahoveanu et al., 1986 ). An intriguing observation is the presence of anti-influenza activity in a wide variety of phytochemicals, such as alkaloids, flavonoids, glucosides, polyphenols, saponins (Wang et al., 2006) . It is being hoped that in near future, we will be able to see an effective phytochemical for controlling the influenza virus.

Although exposure to any of these viruses leads to acute infection, however, type B, C, and D are unique in causing chronic infection. Traditional medicine for viral hepatitis has mainly focused on plants belonging to the genus Phyllanthus of the Euphorbiaceae family. Clinical studies were also designed to compare anti-hepatitis B effects for different species of Phyllanthus, i.e. P. amarus (L.), P. niruri (L.) and P. urinaria (L.) (Wang et al., 1995) . Molecular studies on antiviral potentials of P. amarus (L.) showed its inhibitory effect on HBV polymerase activity and mRNA transcription due to interactions with HBV enhancer I and C/EBP alpha and beta transcription factors (Lee et al., 1996; Ott et al., 1997) . Microarray analyses revealed the anti-HBV activity of ethanolic extract of another member of Phyllanthus (P. nanus) due to over expression of several genes particularly annexin 7 (Anx7) .

Usually, screening of antiviral compounds has been snagged due to the lack of representative smaller animal model. However, in the case of HBV infection in humans, duck hepatitis B virus (DHBV) model has served as an excellent screening system (Niu et al., 1990 ). The DHBV system has been used for screening anti-HBV effect of various medicinal plants. Based on previous observations, that suggested anti-HBV effect of Phyllanthus species, various members of this plant family were screened for their antiviral effects in DHBV model. Initial findings revealed that Phyllanthus amarus has no significant inhibitory effect on DHBV DNA replication in vivo (Niu et al., 1990) . Further studies compared antiviral activity of P. amarus and P. maderas (Munshi et al., 1993a) , P. maderaspatensis (Munshi et al., 1993b) in DHBV model and concluded that these medicinal plants do not have any therapeutic potential against HBV in humans as previously thought. Although P. nanus, another member of the Phyllanthus genus of plants showed strong inhibitory effect in controlling DHBV in primary cell culture model . Such controversial data need further investigation at molecular level to validate initial clinical data in the DHBV model. Besides resolving initial observation relevant to therapeutic development of Phyllanthus species plants, DHBV model has been very helpful in identifying a number of other plants which could be potentially utilized for isolation of candidate therapeutics for appropriate clinical trials. For example screening of 56 different Chinese medicinal herbs led to the identification of two potentials anti-DHBV plant extracts, i.e. Ardisia chinensis, and Pithecellobium clypearia . The identification of anti-HBV potentials of Oenanthe javanica Blume DC flavones (OjF), as a strong inhibitor of HBsAg and HBeAg secretion (involved in viral pathogenesis) in 2.2.15 cells and reducing DHBV-DNA levels in the HBV-infected duck model is also credited to this valuable model .

Sometimes several medicinal plants are mixed together to develop a combination therapy for treating a particular ailment. For viral hepatitis such combination therapies have also been tried. For example, liquid fermentation broth of Ganoderma lucidum on supplementation with aqueous extract of Radix Sophorae flavescentis (Chinese herbal medicine) showed strong anti-hepatitis B virus activity in vitro and in vivo. Furthermore, co-fermentation of both these medicinal plant for the development of antiviral broth showed superior antiviral effect compared with simple mixing .

Hepatitis C is another member of the viruses causing viral hepatitis. A study reviewed the beneficial and adverse effects of herbal preparations used for the treatment of viral hepatitis in the Cochrane Collaboration, MEDLINE, EMBASE, and BIO-SIS databases. Data from manual searches for five Chinese and one Japanese journals were also included besides information from randomized clinical trials (Liu et al., 2003) . Evaluation of previously completed 13 randomized trials analysis included in this study showed that only four have appropriate methodologies. Disappointingly, few herbs/phytochemicals used in clinical trials have anti-HCV activity, like Silybin, and Oxymatrine, which showed a significant reduction of serum aspartate aminotransferase (AST) and gamma glutamyltranspeptidase levels and HCV clearance, respectively. A number of Chinese herbal mix such as Bing Gan Tang, Yi Zhu decoction, and Yi Er Gan Tang individually or in combination with antivirals showed beneficial effects on clearing HCV RNA and normalizing serum alanine aminotransferase (ALT). Various herbal products adverse events were also summarized in this information collection report (Liu et al., 2003) . Such reports strongly suggest appropriate vigilance programs as well as involvement of international regulatory agencies for assessing the benefits of herbal medicine.

Screening programs aimed at the identification of anti-HCV medicinal plants are ongoing, particularly due to the prevalence of infection in the resource poor countries and lack of good vaccine. The methanolic extracts of Acacia nilotica L. Willd ex Delile, Boswellia carterii, Embelia schimperi, Quercus infectoria, Trachyspermum ammi L. and aqueous extracts of Piper cubeba L., Q. infectoria and Syzygium aromaticum L., showed potentials to inhibit HCV (Hussein et al., 2000) . Moreover, a number of phytochemical products such as catechin, glycyrrhizin, polysterols, silymarin potentials as anti-HCV agents have also been reviewed (Jassim and Naji, 2003; Patrick, 1999) .

Emerging viral infections are posing a major threat to the mankind. Medicinal plants exhibiting broad antiviral effects could be brought into the antiviral discovery programs for such infection. One such example is Glycyrrhizin, a bioactive component of liquorice (Glycyrrhiza uralensis Fisch), and lycorine isolated from Lycoris radiata L. initially used for certain other indication, showed strong anti-SARS-CoV activity . A number of plants previously shown to possess broad-spectrum antiviral effects could be screened for newly emerging/resistant viral strains.

A variety of herbal (medicinal) preparations have shown potentials for inhibiting viruses causing serious infections among humans such as measles viruses (Olila et al., 2002; Sindambiwe et al., 1999) , human rotaviruses (HRV) (Husson et al., 1994; Takahashi et al., 2001) , respiratory syncytial virus (RSV), human rhinoviruses (Glatthaar-Saalmuller et al., 2001) , coxsackie group of viruses (Evstropov et al., 2004; Su et al., 2006) , neurotropic Sindbis virus (NSV) (Paredes et al., 2001) and various strains of poliovirus (Andrighetti-Frohner et al., 2005; Melo et al., 2006; Vilagines et al., 1985) . To prove/disprove antiviral effect of any herbal preparation it is essential to molecularly dissect its effects. Very few studies have addressed this important aspect relevant to the therapeutic development of phytochemicals. One such example is the molecular study of the hot water extracts of Stevia rebaudiana L. which blocked entry of various infectious serotypes of HRV into the permissive cells by an anionic polysaccharide having a molecular weight of 9800 with uronic acid as a major sugar constituent (Takahashi et al., 2001) . Similarly an alkaloid extract of Haemanthus albiflos bulbs inhibited RNA synthesis of HRV propagated in MA-104 cells (Husson et al., 1994) .

Based on all the above information, it can be fairly concluded that medicinal plants offer a variety of anti-infectious compounds, particularly antiviral agents. Screening programs aimed at identifying potential anti-infectious agent from medicinal plants offer a great potential in the field of pharmaceutical developments.

The very first and basic step towards evaluating the therapeutic potential of a medicinal plant is preparation of crude cellular lysate of the plant matrix followed by extraction of various components having potential medicinal value. There are several books and reviews describing standardized extraction procedures from medicinal plants. A few to start with could be: Plant Drug Analysis: A Thin Layer Chromatography Atlas (Wagner et al., 1996) , Modern Phytomedicine: Turning Medicinal Plants into Drugs (Ahmad et al., 2007) and Laboratory Handbook for the Fractionation of Natural Extracts (Houghton and Raman, 1998) . Most of the books published in phytomedicine have mainly paid attention to classical isolation procedures. Unfortunately, some of these classical procedures have limitations of reproducibility and quality, thus compromising the safety and efficacy of phytomedicinal preparations. As such there is an urgent need to refine and further develop classical methodologies to obtain procedural consistency and highly pure plant components exhibiting medicinal value. In recent past, increased interest in traditional medicine has complemented quality awareness and refinement in extraction methodologies and standardization of procedures for phytochemedicinal products isolation (Atta-ur-Rahman and Choudhary, 1998; Ong, 2004) .

To ensure high quality herbal preparations, efforts are ongoing to replace traditional methodologies with modern sample preparation and extraction procedures. Classical solvent separation of phytomedicinal products is being complemented with modern techniques like microwave-assisted extraction, pressurizedliquid extraction, matrix-assisted laser desorption/ionization mass spectrometry (Wu et al., 2007) and several others. To further facilitate plant-based drug discovery efforts are also being directed toward standardization of methodologies which can be used to study pharmacokines/pharmacodynamics behavior of phytomedicinal products .

The importance of medicinal plants can be ascertained from the fact that according to the World Health Organization (WHO) estimates, 80% of the World's population fulfills their healthcare needs from phytomedicinal sources (2005a) . Programs aimed at inclusion of medicinal plants into the healthcare need of the people should be sponsored in countries where plants and their products are practiced for medical needs. The countries having heavy usage of traditional medicine should sponsor scientific programs devoted toward modern drug discovery from phytochemicals. Improved separation technologies offer potentials to screen medicinal plant's anti-infectious/antiviral nature. Several problems previously thought to be hurdle in the medicinal plants antiviral drug discovery program are no longer an issue. For example screening of the antiviral potentials of plant extracts always posed a threat of incidental infection to the workers. Vector-based assay techniques have been very helpful in overcoming such screening hurdles, i.e. recombinant viral vectors mimicking the infection and expressing firefly luciferase marker gene have been widely used to screen a variety of antivirals (Esimone et al., 2005) .

A clever usage of plants is the production of vaccines and protein-based therapeutics. Several scientific reports suggest that plant could offer a good source for the production of pharmaceutical grade peptides/proteins (Glenz and Warzecha, 2006; Koprowski and Yusibov, 2001) . Since the expression of first subunit vaccine for HBV surface antigen in 1992, several other different vaccine antigens have been successfully expressed in plants and their safety has been assessed in animal and humans (Glenz and Warzecha, 2006; Ma et al., 2003; Thanavala et al., 2005) . While considering this aspect of plants for treating human viral diseases one has to be careful, as majority of viral vaccines are constituted of attenuated or inactivated viral particles. Due to these limitations efforts have been directed toward expressing coat proteins of different viruses which are presumed to assemble as virus-like-particles (VLP) in plants and are antigenic in nature. Several other issues like appropriate processing of protein to be expressed in plants are important aspects to be considered.

There are other issues to be resolved before the translational usage of medicinal plants in the developed world. One such issue is the isolation of active ingredient associated with the medicinal characteristics of a particular plant. In certain parts of the world crude plant extracts are used in healthcare and their efficacy is well-documented without any side effects. Although it will be hard to get these plant extracts approved through international regulatory agencies such as the Food and Drug Administration (FDA) of the United States of America or other equivalent European counterparts, however, for coun-tries with limited resources, government sponsored explorations will serve as a gateway for merging of modern drug discovery with conventional Chinese/Eastern medicine. Moreover, considering the problems faced by the developed world such as drug resistance and failure in finding an effective vaccine for deadly infectious agent such as HIV, a causative agent for deadly AIDS, phytomedicinal products may provide a hope.

Although, herbal (medicinal plants) preparations are widely used in several parts of the world, individually or in combination, data about the interactions of medicinal plants on living system is non-existent. It is only experience of the indigenous people using a particular plant/phytochemical product for treating an ailment. Clinical findings such as co-administration of medicinal plants kava-kava and St. John's Wort leading to hepatotoxicity (Musch et al., 2006) should be made available to the healthcare providers practicing traditional medicine. Generally, herbal remedies are perceived as harmless, however, several reports suggest hepatotoxicity associated with herbal medication (Pak et al., 2004; Schiano, 2003) . Publication of scientific reports relevant to the cytotoxicities of medicinal plants usage should be encouraged and incorporated into a universal database system. Moreover, larger randomized, double-blind, placebo-controlled multicenter clinical trials should be conducted before incorporation of a particular herbal remedy in treating people.

116 8. Isolation and characterization of plant components exhibiting medicinal characteristics

Future directions in antiviral potentials of medicinal plants

Medicinal plants-time to harness the potential of neglected genetic resources? Plant Genetic Resources: Characterization and Utilization

Anti-HIV activity against immunodeficiency virus type 1 (HIV-I) and type II (HIV-II) of compounds isolated from the stem bark of Combretum molle

New natural products from medicinal plants of Pakistan

The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines

Cyanovirin-N binds to the viral surface glycoprotein, GP120 and inhibits infectivity of Ebola virus

An investigation of the antiviral activity of Podophyllum peltatum

Further screening of Venda medicinal plants for activity against HIV type 1 reverse transcriptase and integrase

Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development

Antiviral activity of hop constituents against a series of DNA and RNA viruses

Virucidal activity presence in Trichilia glabra leaves

Ethanol extract of Polygonum cuspidatum inhibits hepatitis B virus in a stable HBV-producing cell line

The action of plant extracts on a bacteriophage of Pseudomonas pyocyanea and on influenza A virus

In vitro cytotoxic, antiviral and immunomodulatory effects of Plantago major and Plantago asiatica

Botanical sources of influenza inhibitors

Emerging anti-HIV drugs

Antiviral activity of Chamaecyparis lawsoniana extract: study with herpes simplex virus type 2

In vitro pharmacodynamic evaluation of antiviral medicinal plants using a vector-based assay technique

Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120

Anti-enterovirus and immunostimulating activity of the polyphenol complex extracted from Pethaphylloides fruticosa

Antiviral effect of Guazuma ulmifolia and Stryphnodendron adstringens on Poliovirus and Bovine Herpesvirus

Compounds from rose (Rosa rugosa) flowers with human immunodeficiency virus type 1 reverse transcriptase inhibitory activity

Antiviral activity of an extract derived from roots of Eleutherococcus senticosus

New medicinal plants for the production of vaccines

Medicinal plants: a re-emerging health aid. Electr

Laboratory Handbook for the Fractionation of Natural Extracts

Inhibition of hepatitis B virus production by Boehmeria nivea root extract in HepG2 2.2.15 cells

Molecular targets of anti-HIV-1 triterpenes

Inhibitory effects of Sudanese medicinal plant extracts on hepatitis C virus (HCV) protease

Inhibitory effects of Sudanese plant extracts on HIV-1 replication and HIV-1 protease

Study of antiviral action of total alkaloids from Haemanthus albiflos

A plant polyphenol-rich extract restores the suppressed functions of phagocytes in influenza virus-infected mice

Novel antiviral agents: a medicinal plant perspective

Baicalin, an inhibitor of HIV-1 production in vitro

The green revolution: plants as heterologous expression vectors

Coumarins as inhibitors of HIV reverse transcriptase

Anti-HIV, anti-Poxvirus, and anti-SARS activity of a nontoxic, acidic plant extract from the Trifollium Species Secomet-V/anti-Vac suggests that it contains a novel broad-spectrum antiviral

Inhibition of hepatitis B virus by an aqueous extract of Agrimonia eupatoria L

Antiviral effect of Phyllanthus nanus ethanolic extract against hepatitis B virus (HBV) by expression microarray analysis

Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication

Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment

In vitro antiviral activities of Chinese medicinal herbs against duck hepatitis B virus

Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry

Anti-hepatitis activities in the broth of Ganoderma lucidum supplemented with a Chinese herbal medicine

Simultaneous determination of glycyrrhizin, a marker component in radix Glycyrrhizae, and its major metabolite glycyrrhetic acid in human plasma by LC-MS/MS

Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials

The production of recombinant pharmaceutical proteins in plants

Antiviral effect of aqueous plant extracts in tissue culture

The in vitro antivirial activity of an aliphatic nitro compound from Heteropteris aphrodisiaca

The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV)

Phytochemical screening and antiviral activity of some medicinal plants from the island Soqotra

Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection

Evaluation of antihepadnavirus activity of Phyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks

Acute hepatitis due to kavakava and

Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo

Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo

Screening extracts of Zanthoxylum chalybeum and Warburgia ugandensis for activity against measles virus (Swartz and Edmonston strains) in vitro

Extraction methods and chemical standardization of botanicals and herbal preparations

Purification and characterization of a new antiviral protein from the leaves of Pandanus amaryllifolius

Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors

Hepatotoxicity of herbal remedies: an emerging dilemma

Biologically active constituents of a polyphenol extract from Geranium sanguineum L. with anti influenza activity

Biological activity of Guatteria cardoniana fractions

Inhibitory potential of neem (Azadirachta indica Juss) leaves on dengue virus type-2 replication

Anti-HIV protease activity from rosa family plant extracts and rosamultin from Rosa rugosa

Hepatitis C: epidemiology and review of complementary/alternative medicine treatments

Glycyrrhizic acid inhibits virus growth and inactivates virus particles

Prophylactic effect of a Beta vulgaris extract on experimental influenza infection in mice

Bioactive deoxypreussomerins and dimeric naphthoquinones from Diospyros ehretioides fruits: deoxypreussomerins may not be plant metabolites but may be from fungal epiphytes or endophytes

Hepatotoxicity and complementary and alternative medicines

Anti-infective activity of a plant preparation from Geranium sanguineum L

Influenza virus variants with reduced susceptibility to inhibition by a polyphenol extract from Geranium sanguineum L

Screening of seven selected Rwandan medicinal plants for antimicrobial and antiviral activities

Emerging issues in traditional Chinese medicine. Can

Antiviral activity and constituent of Ardisia chinensis benth against coxsackie B3 virus

Analysis of anti-rotavirus activity of extract from Stevia rebaudiana

Immunogenicity in humans of an edible vaccine for hepatitis B

Anti-viral activity of the extracts of a Kenyan medicinal plant Carissa edulis against herpes simplex virus

Herbal medicines for sexually transmitted diseases and AIDS

Inhibition of poliovirus replication by an extract of Matricaria chamomilla (L)

Plant Drug Analysis: A Thin Layer Chromatography

Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites

Zinc coupling potentiates anti-HIV-1 activity of baicalin

Effect of Oenanthe javanica flavone on human and duck hepatitis B virus infection

Anti-influenza agents from plants and traditional Chinese medicine

Immunostimulant properties of Heracleum maximum Bartr

Resistance of human immunodeficiency virus type 1 to the high-mannose binding agents cyanovirin N and concanavalin A

In vitro HIV type 1 reverse transcriptase inhibitory activities of Thai medicinal plants and Canna indica L. rhizomes

Direct analysis of alkaloid profiling in plant tissue by using matrix-assisted laser desorption/ionization mass spectrometry

Antiviral activity of a hot water extract of black soybean against a human respiratory illness virus

The in vitro activity of geraniin and 1,3,4,6-tetra-O-galloyl-beta-d-glucose isolated from Phyllanthus urinaria against herpes simplex virus type 1 and type 2 infection

Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents

The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections

Inhibition of HIV replication by baicalin and S. baicalensis extracts in H9 cell culture

In vitro anti-HCV activities of Saxifraga melanocentra and its related polyphenolic compounds