anti viral drugs

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plant remedy for viral diseases.

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ANTIVIRAL DRUGS Prepared by S.Nirmala., M.Pharm.,(Ph.D) : 

ANTIVIRAL DRUGS Prepared by S.Nirmala., M.Pharm.,(Ph.D)

Slide 2: 

Virus Vs Natural drugs ANTIVIRAL DRUGS

General Characteristics of Viruses : 

General Characteristics of Viruses Depending on one's viewpoint, viruses may be regarded as exceptionally complex aggregations of nonliving chemicals or as exceptionally simple living microbes. Viruses contain a single type of nucleic acid (DNA or RNA) and a protein coat, sometimes enclosed by an envelope composed of lipids, proteins, and carbohydrates. Viruses are obligatory intracellular parasites. They multiply by using the host cell's synthesizing machinery to cause the synthesis of specialized elements that can transfer the viral nucleic acid to other cells.

Host Range : 

Host Range Host range refers to the spectrum of host cells in which a virus can multiply. (narrow vs. broad) Most viruses infect only specific types of cells in one host species, so they do not generally cross species barriers. Host range is determined by the specific attachment site on the host cell's surface and the availability of host cellular factors

Viral Structure : 

Viral Structure A virion is a complete, fully developed viral particle composed of nucleic acid surrounded by a coat. Helical viruses (for example, Ebola virus) resemble long rods and their capsids are hollow cylinders surrounding the nucleic acid. Polyhedral viruses (for example, adenovirus) are many-sided. Usually the capsid is an icosahedron. Enveloped viruses are covered by an envelope and are roughly spherical but highly pleomorphic (for example, Poxvirus). There are also enveloped helical viruses (for example, Influenzavirus) and enveloped polyhedral viruses (for example, Herpesvirus). Pleomorphic: Many-formed. A tumor may be pleomorphic. Complex viruses have complex structures. For example, many bacteriophages have a polyhedral capsid with a helical tail attached. Bacteriophage: A virus that infects and lyses certain bacteria.

Schematic of Influenza Virus : 

Schematic of Influenza Virus

RETRO VIRUS : 

RETRO VIRUS

Influenza virus : 

Influenza virus

Nucleic Acid : 

Nucleic Acid Viruses contain either DNA or RNA, never both, and the nucleic acid may be single- or double-stranded, linear or circular, or divided into several separate molecules. The proportion of nucleic acid in relation to protein in viruses ranges from about 1% to about 50%.

DNA viruses : 

DNA viruses Gene expression is much like that of the host cell DNA-dependent RNA polymerase synthesizes mRNA Host cell ribosomes and tRNAs used to translate viral mRNA Unique viral proteins include structural proteins and replication enzymes for viral DNA. Example-Herpesvirus, Epstein-Barr (mononucleosis

RNA viruses : 

RNA viruses Cells cannot make copies of RNA. Three kinds of strategies for RNA viruses:

Anti viral drugs : 

Anti viral drugs

Anti viral drugs : 

Anti viral drugs

NATURAL ANTIVIRAL DRUGS : 

NATURAL ANTIVIRAL DRUGS Glycyrrhizin Gossypol Hypericin Inophyllum B Calanotide A&B Vidarabine

Glycyrrhizin : 

Glycyrrhizin Glycyrrhizin is the main sweet-tasting compound from liquorice root. B.S: GLYCYRRIHA GLABRA FAMILY: GLYCYRRACEAE It is 30–50 times as sweet as sucrose (table sugar). Pure glycyrrhizin is odorless

Structure of glycyrrhizin : 

Structure of glycyrrhizin (3β,18α)-30-hydroxy-11,30-dioxoolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronic acid

Other names : 

Other names Glycyrrhizin Glycyrrhizinic acid Glycyrrhizic acid Glycyrrhetinic acid glycoside(3-beta,20-beta)-20-Carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid Ammonium salt Monoammonium glycyrrhizinate (MAG)Magnasweet

Therapeutic application of glycyrrhizin : 

Therapeutic application of glycyrrhizin Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and "flu-like" symptoms.

Slide 19: 

Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases.

Slide 20: 

study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon.(Ashfaq et al 2011)

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glycyrrhizin were tested in vitro for their antiviral activities against 11 pathogenic flaviviruses belonging to principal antigenic complexes or individual serogroups of medical importance: dengue, Japanese encephalitis, mammalian tick-borne and yellow fever virus (YFV) groups.

Slide 22: 

Glycyrrhizin inhibited the replication of flaviviruses at high non-cytotoxic concentrations(crance et al 2003) Glycyrrhizin inhibits Influenza A virus uptake into the cell.

Slide 23: 

Glycyrrhizin, a triterpenoid glycoside and Licorice from Glycyrrhiza glabra and Ammonium salt of Glycyrrhizic acid (Sigma) were tested for antiviral activity on three strains of Japanese encephalitis virus (JEV), Nakayama, P-20778 and 821564 XY48. Purified glycyrrhizin (M.w. 822.92) inhibited plaque formation in all the three strains of JEV at a concentration of 500 micrograms/ml at 96 hrs, Similar effect was observed at 1000 micrograms/ml concentration with Licorice and Ammonium salt of glycyrrhizic acid. The minimal inhibitory concentrations were not toxic to porcine stable kidney (PS) and human cervical carcinoma (HeLa) cell lines.(Badam et al 1997)

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glycyrrhizin (GL) was investigated for its antiviral action on varicella-zoster virus (VZV) in vitro. When human embryonic fibroblast (HEF) cells were treated with GL after inoculation of virus (post-treatment), the average 50%-inhibitory dose (ID50) for five VZV strains was 0.71 mM, and the selectivity index (ratio of ID50 for host-cell DNA synthesis to ID50 for VZV replication) was 30. GL was also effective against VZV replication when HEF cells were treated 24 h before the inoculation (pretreatment). (Baba M& Shigeta S 1987)

Slide 25: 

Glycyrrhizin and glycyrrhetinic acid exhibit similar properties and have been shown to be effective for Hepatitis A, B, C; HIV; herpes (I, II, zoster (shingles virus), perhaps 6); lichen planus, influenza, CMV (cytomegalovirus) and cancer. Personal experience and reports of effectiveness show it is effective against chronic fatigue immune deficiency syndrome (CFIDS) and the viruses associated with this condition (EBV (Epstein-Barr) virus, CMV), condyloma (genital wart virus) and other "viral" presentations.1-5

Glycyrrhizin and HIV : 

Glycyrrhizin and HIV AIDS patients with high CD4/CD8 ratios (also known as helper cell/suppressor cell ratios) improved significantly with SNMC (5 mg glycyrrhizin /kg). Almost half the patients improved during treatment. Glycyrrhizin inhibited viral replication and had interferon-inducing, natural-killer-cell enhancing effects. Glycyrrhizin inhibits HIV replication in cultures of cells from HIV-infected patients. In 31 percent of samples, glycyrrhizin inhibited more than 90 percent of HIV replication.

Slide 27: 

glycyrrhizin is used in the treatment of upper respiratory infections. Vesicular stomatitis, Flaviviruses, respiratory syncytial virus, Kaposi sarcoma-associated herpes virus and H. pylori. Glycyrrhizin is known to exert antiviral and anti-inflammatory effects.

Gossypol vs herpes simplex virus type II : 

Gossypol vs herpes simplex virus type II Gossypol, a disequiterpene obtained from cottonseed oil, and a series of peri-acylated gossylic nitriles were compared for their antiviral activities against HSV-II and for their toxicities to the host Vero cells. All of the peri-acylated gossylic nitriles exhibited lower cytotoxicities to the host cell than did the parent compound gossypol. Pharmacol Res Commun. 1986 Nov;18(11):1063-73. Antiviral activities of gossypol and its derivatives against herpes simplex virus type II. Radloff RJ, Deck LM, Royer RE, Vander Jagt DL.

Slide 29: 

Both gossypol and the series of derivatives exhibited antiviral activities against HSV-II when the virus was treated with drug at concentrations as low as 5 X 10(-7) M. Two of the derivatives, gossylic nitrile-1,1'-diacetate and gossylic nitrile-1,1'-divalerate, were capable of inhibiting viral multiplication in Vero cells that were infected with virus before administration of the drug.

Inactivation of human immunodeficiency virus in vitro by gossypol : 

Inactivation of human immunodeficiency virus in vitro by gossypol Following exposure of cell-free incubates of HIV to 100 uM gossypol, ultracentrifugation and inoculation of the washed pellet onto H9 cells, there is no evidence of elevated reverse transcriptase activity over 21 days. Treatment with lower concentrations of gossypol reduces the peak and lengthens the time to maximal reverse transcriptase activity compared with control cultures.

Slide 31: 

observations suggest that gossypol could be used as a vaginal spermicidal/virucidal agent Gossypol is an orally active male anti-fertility agent that has been used in China by more than 10,000 men. Its biological abilities and effects include both anti-viral and anti-parasitic activity. virucidal activity has been observed against many diseases including herpes simplex-2.

Hypericin : 

Hypericin B.S: St John's wort is the plant species Hypericum perforatum, and is also known asTipton's Weed, Chase-devil, or Klamath weed. Family: Hypericaceae

Hypericin : 

Hypericin Hypericin is a naphthodianthrone, a red-colored anthraquinone-derivative, which, together with hyperforin, is one of the principal active constituents of Hypericum(Saint John's wort).  Hypericin is believed to act as an antibiotic and non-specifickinase inhibitor.

Hypericin : 

Hypericin Hypericin may inhibit the action of the enzyme dopamine β-hydroxylase, leading to increased dopamine levels, although thus possiblydecreasing norepinephrine and epinephrine. The crude extract of Hypericum is a weak inhibitor of MAO-A and MAO-B  Isolated hypericin does not display this activity, but does have some affinity for NMDA receptors. This points in the direction that other constituents are responsible for theMAOI effect.

Hypericin structure : 

Hypericin structure IUPAC name 1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione

Anti viral property of hypericin : 

Anti viral property of hypericin Hypericin is a natural derivative of the common St. Johns wort plant,Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV).  Hypericin, an anthraquinone dimer previously shown to have activity against nonhuman retroviruses also exhibited anti-HIV-1 activity in lymphocytes. Some of the active anthraquinones inhibited HIV-1 reverse transcriptase. H

Anti viral property of hypericin : 

Anti viral property of hypericin The antiviral and antineoplastic activities of hypericin and its derivatives and its mode of action have been widely studied, in the last two decades.  Hypericin heteroassociations with biological macromolecules, DNA and human serum albumin in particular. An alternative type of the hypericin photosensitizing activity associated with its ability to produce a photogenerated pH drop is discussed that and discussed in connection with its potential application in photodynamic therapy.

Anti viral property of hypericin : 

Anti viral property of hypericin In vivo, hypericin (50 mg/ml) was effective against FLV or HSV-1 if incubated with the virus for 1 h at 37°C before infecting mice, but was not effective if pre-incubated with virus for 1 h at 4°C or if administered concurrently with virus. Hypericin decreased cell motility significantly in established lines, T98G and U87-MG, and also in a low-passage human malignant glioma cell line.

Inophyllum B : 

Inophyllum B Biological source Calophyllum inophyllum Linn (Syn. Calophyllum bintagor Roxb.) (Guttiferae). It is a member of the mangosteen Family. Mesuaferrea Linn

Inophyllum B : 

Inophyllum B

Uses : 

Uses HIV-1  Inhibit P. aeruginosa and Bacillus subtili

Calanotide A& B : 

Calanotide A& B Biological source Calophyllum lanigerum Family : Clusiaceae

Slide 43: 

Calanotide A Calanotide B

Uses : 

Uses varicella zoster virus, Epstein Barr virus, influenza A and B,  HIV

Vidarabine : 

Vidarabine Vidarabine or adenine arabinoside is an antiviral drug Biological source: Ecteinascidia turbinata

Vidarabine structure : 

Vidarabine structure

Applications : 

Applications VIDARABINE - OPHTHALMIC OINTMENT  for eye infections Anti-cancer drug. Act against  Herpes virus infection in man Vidarabine (9-β-D-ribofuranosyladenine) is an analog of adenosine with the D-ribose sugar, replaced with D-arabinose

AIDS : 

AIDS Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is an immunosuppressive disease that results in life-threatening opportunistic infections and malignancies. Despite continuous advances made in antiretroviral therapy, AIDS has become the leading cause of death in Africa and fourth worldwide; the number of people with HIV is increasing at an alarming rate in India and Southeast Asia.

Slide 50: 

Biodiversity of the plant kingdom has always provided a source of new drug candidates for almost all disease areas. The number of compounds exhibiting anti-HIV activity and isolated from natural sources is increasing steadily Ex: Calanolide A, a coumarin isolated from Callophyllum lanigerum and two other natural product-derived molecules, DSB and 3-hydroxymethyl- 4-methyl DCK are phase II clinical candidates, with potential to come up as drugs for treatment of HIV infection.

Types of HIV virus : 

Types of HIV virus Two major types of HIV have been identified so far, HIV-1 and HIV-2. HIV-1 is the cause of the worldwide epidemic and is most commonly referred to as HIV. It is a highly variable virus, which mutates readily. There are many different strains of HIV-1, which can be classified according to groups and subtypes; there are two groups, M and O. Within group M, there are currently known to be at least ten genetically distinct subtypes of HIV-1. HIV-2 is much less pathogenic and occurs rarely; it is found mostly in West Africa3.

Alkaloids : 

Alkaloids

Coumarins : 

Coumarins

Flavonoids : 

Flavonoids

Lignans : 

Lignans

Phenolics : 

Phenolics

Others : 

Others Quinones Saponins Terpenes/sterols Xanthones Carbohydrates Peptides Proteins Also acting against the retro virus

Slide 58: 

Thank you

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