Antiviral activity against

In the area of medicinal chemistry, Haemers and coworkers synthesized a series of 4 -hydroxy-3-methoxyflavones that exhibited antiviral activity against poliomyelitis and rhinoviruses. A representative number of compounds is shown below. First, O-hydroxyacetophenones 61 were converted to the corresponding flavones 64 using standard conditions in yields of 74-92%. Cleavage of the benzyloxy groups of 64 was then achieved under acidic conditions to deliver the requisite flavones 65. 

Lemon balm isa perennial herb with heart-shaped leaves that has been used for hundreds of years. Its scientific name is Melissa officinalis. Traditionally the herb has been used for Graves disease (see Chap. 51), asa sedative, arrtispasmodic, and an antiviral agent. When used topically, lemon balm has antiviral activity against herpes simplex virus(HSM). No adverse reactions have been reported when lemon balm is used topically. 

Matthews DA, Dragovich PS, Webber SE, Fuhrman SA, Patick AK, Zalman LS, Hendrickson TF, Love RA, Prins TJ, Marakovits JT, Zhou R, Tikhe J, Ford CE, Meador JW, Ferre RA, Brown EL, Binford SL, Brothers MA, DeLisle DM, Worland ST (1999) Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc Natl Acad Sci USA 96 11000-11007... 

IFN-y exhibits antiviral activity against HBV in vitro (Parvez et al. 2006). In addition, IFN-y was fonnd to rednce hepatic fibrosis by 63% after 9 months, compared to 24% in nntreated controls (Weng et al. 2005). 

Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR (2006) Lambda interferon (IFN-lambda), a type III lEN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80 4501 509... 

Ribavirin is a guanosine analog synthesized more than 35 years ago, which possesses broad-spectrum antiviral activity against several RNA and DNA viruses in vitro (Sidwell et al. 1972). When administered as monotherapy in patients with chronic hepatitis C, ribavirin induces a decline of serum alanine aminotransferase (ALT) levels while no effect on sustained virologic response is detectable (Di Bisceglie et al. 1992). 

Hewson CA, Jardine A. Edwards MR. Laza-Stanca V, Johnston SL Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. J Virol 2005 79 12273-12279. 

Extensive investigations have been performed related to the synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylamino-pyrimidines and -pyridines are strong stimulants of mmor necrosis factor-a (TNF-a) [132]. TNF is a substance that can improve the body s namral response to cancer by killing cancer cells. Another example is 1,6-diaminodiamantane [87], which possesses an antitumor and antibacterial activity. Also, many derivatives of aminoadamantanes have antiviral activity like 3-(2-adamantyl) pyrolidines with two pharmacophoric amine groups, which have antiviral activity against influenza-A virus [133]. 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

Schwendener RA, et al. New lipophilic acyl/alkyl dinucleoside phosphates as derivatives of 3 -azido-3 -deoxythymidine Inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens. Antivir Res 1994 24 79. 

Reports on the antiviral activity of flavanones isolated from medicinal plants have also been found in the literature. Two new antiviral flavanone derivatives were isolated from a methanol extract of leaves of Pithecellobium clypearia (Jack.) Benth (Fabaceae), guided by antiviral assays.The structures were characterized as 7-0-galloyltricetifavan (Fig. 14) and 7,4 -di-0-galloyltricetifavan. CPE reduction assay showed that both compounds possess antiviral activity against respiratory syncytial virus, influenza A HlNl virus, CVB3 and HSV-1. Examples of other... 

A number of l-aryl-6-aminouracils (LIX Ar = fluoro- or trifluoromethyl-substituted phenyl, X = H, NO or NHj) were found to possess antiviral activity against rhinovims 1059. Among these, l-(OT-trifluoromethylphenyl)-5,6-diamino-uracil (LIX Ar = W-CF3, X = NH2), possesses antibacterial activity against Bacillus subtilis, Staph, aureus zni Mycobacterium smegmatis [410]. 

However, the nucleoside analogue 164 was found to be devoid of activity against HSV-1, HSV-2, VZV and the cytomegalovirus (CMV) in human fibroblast (MRC-5) cells. In this case the decreased conformational flexibility resulting from the introduction of the cyclopropyl group into 164 appeared to be unfavourable for interaction with the enzymes involved (vide supra. Sect. 2.9) [222]. Likewise, the cyclopropylpyrimidine 166c-f and 167, the cyclopropyl-purine nucleosides 168 showed no antiviral activity against HSV-1, HSV-2, HCMV and HIV-1 in cell culture, Eq. (66) [223]. 

In addition, the results of biological tests of the compounds synthesized showed that only one possessed the high antiviral activity against adenovirus type 23 and several of them had moderate-to-week activities towards Gram-positive bacteria and pathogenic fungi, whereas the rest of compounds were inactive. 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

EO of Melaleuca alternifolia and eucalyptus exhibited a high level of antiviral activity against Herpes simplex virus type 1 (HSV-1) and Herpes simplex virus type 2 (HSV-2) in a viral suspension test [125]. Also, Santolina insularis EO... 

The 7-pyrrolyl(indolyl)triazolopyrimidinium salts show antiviral activity against herpes simplex 1 and ospoviruses, and against classical avian plaque (90KFZ41). Compound 276 was prepared as a bolting inhibitor for sugar... 

A series of macrolides bearing a thiazole moiety have been isolated from tunicates and sponges. The tunicate Lissoclinum patella has afforded the patellazoles A-C (428-430), which were found to be potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3—10-6 pg/ml as well as exhibiting antifungal activity [334, 335]. Furthermore, patellazole B (429) exhibited very potent antiviral activity against Herpes symplex viruses [334],... 

The majority of antiviral drugs which are under clinical development today generally interrupt viral nucleic acid synthesis. These compounds often do not affect host cell metabolism and possess considerable selectivity against virus-induced enzymes. This article discusses agents exhibiting significant antiviral activity against viral infections in animal model systems. 

Benefits Echinacea is held to be one of the most effective detoxifying herbs in Western medicine for a range of ailments, and is now used in ayurvedic medicine. The polyynes and cichoric acid components are reported to have antibacterial and virostatic effects. Echinacea also demonstrates an anti-inflammatory effect due to the alkamides component. As an immune stimulant, it significantly raises immunoglobulin M levels. Antiviral activities against both the Herpes simplex virus Type I and the influenza-A virus have been observed. 

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