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Antiviral agents

Related article: Palliative vs. curative treatments

By definition, antiviral agents are drugs used in the prophylaxis or therapy of virus diseases. However, the drugs have been used in a wide range of conditions from acute infections such as influenza to chronic inflammatory diseases such as chronic fatigue syndrome. Antivirals have profound effects on the immune system as well as a number of serious adverse effects. Routine use is generally contraindicated for Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) patients. The decision to use antivirals is one which patients should make with their physicians in light of known side effects, contraindications and personal risk of effects from the flu.

Effect on the immune system

For many conditions, antiviral drugs alleviate symptoms of disease.1) However, this could be due to its effect on the immune response. Not enough is known about how exactly antivirals interact with the immune system, but certain preliminary indications strongly suggest that the drugs interfere with immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed.. This suggests that use of the drugs may delay recovery from chronic inflammatory disease.

The reported molecular actions of ganciclovir (Cytovene and Cymevene) may be telling.

During ganciclovir treatment of an adolescent ependymoma patient two weeks after intracranial implantation of HSVtk retroviral vector producer cells, increasing numbers of peripheral T- and B-cells were found as well as enhanced T-cell activation and elevated serum levels of interleukin 12 and soluble Fas ligand.

Kramm et al.2)

While antiviral drugs are supposed to treat only a virus, they appear to have profound effects on other immune functions in the human body. For this reason they are contraindicated for MP patients.

Adverse effects

Depending on the drug, antiviral drugs can have a number of side effects. Oseltamivir is somewhat typical. Common adverse drug reactions associated with oseltamivir therapy include: nausea, vomiting, diarrhea, abdominal pain, and headache as well as other neurological and psychiatric conditions.3)

Types of anti-viral treatments

  • acyclovir (Zovirax)
  • famciclovir (Famvir)
  • ganciclovir (Cytovene and Cymevene)
  • osletamivir (Tamiflu) – Drug that interferes with flu viral reproduction. In order for it to be effective, it must be taken within 40 hours of developing the flu.
  • valganciclovir (Valcyte)
  • valcyclovir HCL (Valtrex)
  • zanamivir (Relenza) – The drug is a powder that is inhaled twice a day for five days from a breath-activated plastic device. In order for the treatment to be most effective, patients need to start treatment within two days of the onset of symptoms.

Research in botanicals

For the past several years we have been evaluating natural products as potential cancer chemopreventive agents 4)

This article reviews the common cold and influenza viruses, presents the conventional treatment options, and highlights select botanicals (Echinacea spp., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions.5)

Inhibitory effects of Astragalus membranaceus on herpes simplex virus type 1(HSV-1)6)

Elderberry

Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza.7)

Effect of concentrated juice of elderberry (CJ-E) on the human influenza A virus (IFV).8)

Rubini elderberry liquid extract active against human pathogenic bacteria as well as influenza viruses. 9)

Differences in treatment time and dose of EF extract in infected cells with influenza virus have a marked effect on the efficacy of the herb.10)

Oregano

A blend of Cinnamomum zeylanicum, Daucus carota, Syzygium aromaticum, Origanum vulgare EOs was antifungal to the six Candida strains tested11)

Essential oils (EOs) and some of their main compounds have demonstrated extensive antimicrobial activity in a wide range of food spoilage or pathogenic fungi, yeast and bacteria. 12)

Other Herbs

Lamiaceae is one of the most important herbal families, well known for various biological and medicinal effects of a variety of aromatic spices, including thyme, mint, oregano, basil, sage, savory, rosemary, self-heal, hyssop, lemon balm13)

The application of plant essential oils (EOs) (hyssop and marjoram) was evaluated for inactivation of non-enveloped viruses using murine norovirus and human adenovirus as models. No significant reduction of virus titres (TCID(50)) was observed14)

Olive

This work is the first study that demonstrated an antiviral activity of both olive twigs and DTBP.15)

Antiviral activity of olive leaf extract (OLE) preparations standardized by liquid chromatography-coupled mass spectrometry (LC-MS) against HIV-1 infection and replication.16)

Inhibition of the in vitroA technique of performing a given procedure in a controlled environment outside of a living organism - usually a laboratory. infectivity of the viral haemorrhagic septicaemia virus (VHSV), a salmonid rhabdovirus. 17)

Ginger

Fresh, but not dried, ginger is effective against HRSV-induced plaque formation on airway epithelium by blocking viral attachment and internalization.18)

It is insinuated that ginger may have anti- Avian influenza virus H9N2 potential and its active compounds needs further investigations.19)

Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV.20)

Rainforest plants

This article reviews the chemical composition, pharmacological properties, state of current research, clinical use, and potential antiviral and immunomodulating activity of these and other plants from the Peruvian Amazon.21)

in vitro antiherpetic activity of hydroethanolic extract from barks, purified fractions of quinovic acid glycosides and oxindole alkaloids was evaluated by plaque reduction assay, including mechanistic studies (virucidal, attachment and penetration action). Once exposure to physical agents might lead to reactivation of the herpetic infection, antimutagenic effect (pre-, simultaneous and post-treatment protocols) was also evaluated by Comet assay. 22)

We infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with Dengue fever and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1.23)

Results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts24)

Inhibitors of EBV-EA promoted by TPA in vitro have been shown to be effective anti-tumor promoting agents in laboratory animal models, our results indicate new and potential applications of these herbal remedies as cancer chemopreventive agents since they are already in clinical use in the human population.25)

Canadian folk remedies

Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae), Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae), Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent. (Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L. (Malvaceae), which have been used as folk medicine in Canada, were evaluated for their anti-hepatoma activity on five human liver-cancer cell lines26)

Only glycoside 1 slightly reduced rhinovirus multiplication. All the compounds were able to inhibit vesicular stomatitis virus infection27)

Calendula

The data obtained showed an inhibitory activity in the case of Phyllanthus orbicularis, as well as for the eucaliptus extract. With the guava extract, the activity was lower than in the 2 previous cases, whereas calendula did not show any inhibition to the assayed concentrations 28)

An inhibitory effect against VSV multiplication was observed for all the calendula compounds tested while HRV replication was significantly affected only by compound 3.29)

Upon evaluation of the cytotoxic activity against human cancer cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon cancer, leukemia, and melanoma cells.30)

These results suggested that organic extract of flowers from Calendula officinalis possesses anti-HIV properties of therapeutic interest.31)

Antiviral properties of Calendula (in Russian)32)

Ginger

In this study, aqueous extracts of six raw food materials (flower buds of clove, fenugreek seeds, garlic and onion bulbs, ginger rhizomes, and jalapeño peppers) were tested for antiviral activity against feline calicivirus (FCV) as a surrogate for human norovirus. 33)

The dried rhizomes of Indonesian ginger, Zingiber officinale, were investigated for antirhinoviral activity34)

These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells.. 35)

ginger, thyme, hyssop, and sandalwood oils exhibited high levels of virucidal activity against acyclovir-sensitive strain KOS and acyclovir-resistant HSV-1 clinical isolates and reduced plaque formation significantly.36)

About 15 plant species are known for their use to cure multiple skin diseases. Among these Berberis lyceum, Bergenia ciliata, Melia azedarach, Otostegia limbata, Phyla nodiflora, Prunus persica and Zingiber officinale constitutes major plants.37)

Fresh ginger of high concentration could stimulate mucosal cells to secrete IFN-β that possibly contributed to counteracting viral infection.38)

Garlic

These results suggest that garlic could be used as an alternative treatment for Dengue infection and for the prevention of severe disease development.39)

The theoretical calculations have helped us to determine which active ingredient of the garlic having inhibition effects on HIV-1 and saquinavir.40)

Results revealed that the methanolic and aqueous extracts of garlic were effective in inhibiting promastigote growth of L. tropica41)

A short review of recent patents on antimicrobial effect of garlic.42)

Garlic extract had inhibitory effects on IBV in the chickens embryo43)

Echinacea

Evidence indicates that echinacea potently lowers the risk of recurrent respiratory infections and complications thereof.44)

Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao.45)

Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events46)

These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. super-stimulation (cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. storms).47)

Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio.48)

Virus infection stimulated the release of at least 31 cytokine-related molecules, including several important chemokines known to attract inflammatory cells. Most of these effects were reversed by simultaneous exposure to either of the two Echinacea extracts, although the patterns of response were different for the two extracts.49)

Echinaforce® is efficacious and safe in respiratory tract infections for long-term and short-term prevention as well as for acute treatment.50)

Licorice (glycyrrhizin)

This paper provides a summary of the antiviral and antimicrobial activities of licorice.51)

this study confirms the efficacy of glycyrrhizin in cervical cancer cells which could be an adjunct in the better prevention and management of cervical cancer worldwide.52)

The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.53)

Recently, treatment with a single-tablet regimen containing ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with hepatitis C virus genotype 1 infection who did not respond to prior interferon-based treatment.54)

if the licorice triterpene compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti-HSV1 activity.55)

We believe that dipotassium glycyrrhizinate and ligustrazine hydrochloride can be used to develop a new anti-infectious bursal disease virus compound, and it is worth applying the constituents in clinical practice.56)

Fruit

Suksdorfin (1), which is isolated from the fruit of Lomatium suksdorfii, was found to be able to inhibit HIV-1 replication in the T cell line, H9, with an average EC50 value of 2.6 +/- 2.1 microM. In addition, suksdorfin was also suppressive during acute HIV-1 infections of peripheral blood mononuclear cells, monocyte/macrophages and the promonocytic cell line, U937.. Comparison of the structure and activity of 1 with those of ten related compounds indicated that the dihydroseselin type of pyranocoumarin possessing a 4'-isovaleryl group is important to suksdorfin's enhanced anti-HIV activity.57) (Lomatium belongs to the parsley family)

One hundred methanolic plant extracts were screened for antiviral activity against seven viruses. Twelve extracts were found to have antiviral activity at the non-cytotoxic concentrations tested.58)

Reishi

effects of the aqueous extracts of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum59)

Among 472 patients who underwent oral swabs for gingivitis, 61 patients were positive for HPV16 or HPV18. 60)

Based on the results from the proteomic and sequence alignment analyses, a potentially new immunomodulatory protein (GL18769) was expressed and shown to have high immunomodulatory activity.61)

Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs),62)

The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others.63)

A protein demonstrating laccase activity and potent inhibitory activity towards human immunodeficiency virus (HIV)-1 reverse transcriptase (IC50 1.2 microM) was isolated from fresh fruiting bodies of the medicinal mushroom Ganoderma lucidum. The laccase had a novel N-terminal sequence and a molecular mass of 75 kDa, which is higher than the range (55-56 kDa) reported for most other mushroom laccases.64)

Anti-inflammatory and anti-tumor-promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum.65)

Other

Other commonly used medications, such as inhaled corticosteroidsA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate., oral prednisolone, and Echinacea, also are ineffective in children. Products that improve symptoms in children include vapor rub, zinc sulfate, Pelargonium sidoides (geranium) extract, and buckwheat honey. Prophylactic probiotics, zinc sulfate, nasal saline irrigation, and the herbal preparation Chizukit reduce the incidence of colds in children.66)

Topical and systemic immunotherapy has now found a significant place in the treatment of warts because of its nondestructive action, ease of use, and promising results. 67)

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Notes and comments

A member of ours (SanDiegoJoy) originally “came down” with Sarcoidosis after anti-viral treatment for Hep-C. This is a note to self to look up any words in her posts that explains her experience.

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