Viral activity

Many polysaccharides of eukaryotic origin show non-specific anti-viral activity and this property may be shared by some of the exopolysaccharides. The structural requirements for activity are not immediately evident as the polysaccharides exhibiting this activity are very diverse. 

The suspension of influenza virus, strain A/X-53, was separated from the constituents of alantoic fluid by preparative size exclusion chromatography on a 10 x 120 cm column. The hemo-agglutination method revealed an elevated level (93%) of viral activity. The leakage of the bonded phases can be more efficiently minimized, however, with the use of positively charged polymers. 

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

Hwang DR et al (2006) Synthesis and anti-viral activity of a series of sesquiterpene lactones and analogues in the subgenomic HCV replicon system. Bioorg Med Chem 14(1) 83—91... 

Hamauzu Y, Yasui H, Inno T, Kume C and Omanyuda M. 2005. Phenolic profile, antioxidant property, and anti-influenza viral activity of Chinese quince (Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and apple (Malus domestica Mill.) fruits. J Agric Food Chem 53(4) 928-... 

The answer is b. (Hardman, p 1203.) Trifluridine inhibits viral activity in HSV types 1 and 2, CMV, vaccinia, and perhaps adenovirus. It acts as a viral DNA synthesis inhibitor by irreversibly blocking thymidylate synthetase. Trifluridine triphosphate is a competitive inhibitor of thymidine triphosphate accumulation into DNA It is used in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis caused by HSV 1 and 2. 

Anti-viral activity via receptor different to type-1 IFN... 

Jeong HJ, Ryu YB, Park SJ, Kim JH, Kwon HJ, Kim JH, Park KH, Rho MC, Lee WS. (2009) Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. 

The tubingensins A (379) and B (380) showed activity against the widespread crop pest Heliothis zea, and display in vitro anti-viral activity against herpes simplex virus type 1 with IC50 values of 8 and 9 pg/mL, respectively (346) (see Scheme 2.100). Some bis-basic ethers of carbazoles are anti-viral. When tested against Encephala myocarditis viral infection, several N-ethyl substituted bis-basic carbazoles of the general formula 490 were shown to be active (448) (Scheme 4.9). 

Flavonoids are 15-carbon polyphenols produced by all vascular plants. Well over 4000 distinct flavonoids have now been identified, a limited number of which display therapeutic activity. These substances are generally degraded if taken orally, and are administered medically via the intravenous route. This is probably just as well (the average Western daily diet contains approximately 1 g of flavonoids). A number of flavonoids appear to display anti-viral activity and, hence, are of pharmaceutical interest (Figure 1.12). 

Figure 1.12. Some flavonoids, xanthines and terpenoids. Chrysoplenol B and axillarin are two flavonoids exhibiting anti-viral activity against Rhinovirus (causative agent of the common cold). Examples of xanthines include caffeine and theophylline. Terpenes are polymers of the 5-carbon compound isoprene. Perhaps the best-known such substance discovered in recent years is the diterpenoid taxol, which is used as an anti-tumour agent...

Interferons induce a wide range of biological effects. Generally, type I IFNs induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I IFNs relates to their anti-viral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves but also due to the ability of type I IFNs to increase natural killer (NK) cell and T cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

The molecular basis by which IFNs promote their characteristic effects, particularly anti-viral activity, is understood at least in part. IFN stimulation of the JAK-STAT pathway induces synthesis of at least 30 different gene products, many of which cooperate to inhibit viral replication. These anti-viral gene products are generally enzymes, the most important of which are 2 -5 oligoadenylate synthetase (2, 5-An synthetase) and the eIF-2a protein kinase. 

Interferon gamma is an activator of macrophages. Its anti-viral activity is limited compared to that of interferon alfa. Human recombinant interferon gamma restores, at least in part, macrophage cytotoxicity and with that decreases the incidence of infections in patients with chronic granulomatous diseases. Its adverse effects consist mainly of flu-like syndrome skin rashes may occur. 

As an example ddl (2,3-dideoxyinosine), an inhibitor of the HIV reverse transcriptase (RT-HIV), has an only 30-s half-life at pH 1 (at 37°C). Some formulations allow circumventing the problem of the consequent inefficient oral administration. A chemical alternative consists in the introduction of a fluorine atom in 2j] to disfavour the generation of the oxonium ion involved in the proteolysis (Fig. 16) [57,58], Indeed, the fluorinated analogue is stable in acidic medium while keeping the in vitro anti-viral activity. However, it seems that other problems prevented the clinical development [5,57]. 

Elvucitabine is in phase III development for therapies of HIV and HBV infections. Its anti-viral activity has been shown to result from inhibition of the HIV reverse transcriptase and HBV DNA polymerase (Fig. 35) [99]. 

Mother s milk is an often coined term for products that mimic the natural mother s milk contents. Actual human mother s milk contains about 40-50% casein and 50-60% whey, and about 17% lactoferrin with no beta-lactoglobulin. As I said earlier, mother s milk contains alfa lactoglobulin. This is very different from cow s milk which contains about 80% casein and 20% whey with 1% lactoferrin being average. Lactoferrin has anti-viral activity, and is a potent immune system booster. Obviously this is an advantage for new born human (rug rats) since they lack complete immune system functions. Remember the fact that human mother s milk dominant protein fraction is alfa-lactalbumin Well, there is a research project on going which claims acid folded alfa-... 

On the contrary, lysis and particularly viral lysis could be a major process in these bioassays. In cultures of natural marine bacteria inoculated into 0.2 pm filtered sea water, Wilcox and Furhman (1994) reported that virus abundance increased after few days of bacterial growth. The high abundance and production of bacteria in the HFe bioassay could enhance viral activity and consequently increase specific mortality rates. In agreement with this, during the mesoscale Fe fertilization EISENEX, a higher viral infection of bacterioplankton was estimated in the Fe-enriched patch (Weinbauer et al. 2003). Lysis could be of significance in Fe-limited ecosystems, as Fe released via lysis can be highly bioavailable (Poorvin et al. 2004). 

Bratbak G, Levasseur M, Michaud S, Cantin G, Fernandez E, Heimdal BR, Heldal M (1995) Viral activity in relation to Emiliania huxleyi blooms A mechanism of DMSP release Mar Ecol Prog Ser 128 133-142 Brimblecombe P, Shooter D (1986) Photo-oxidation of dimethylsulfide in aqueous solution. Mar Chem 19 343-353 Brugger A, Slezak D, Obemosterer I, Herndl GJ (1998) Photolysis of dimethylsulfide in the northern Adriatic Sea Dependence on substrate concentration, irradiance and DOC concentration. Mar Chem 59 321-331 Bucciarelli E, Sunda WG (2003) Influence of C02, nitrate, phosphate, and silicate limitation on intracellular dim-ethylsulfoniopropionate in batch cultures of the coastal diatom Thalassiosira pseudonana. Limnol Oceanogr 48 2256-2265... 

Since none of the compounds at the concentrations used showed a complete supression of splenomegaly, one would expect a residual viral activity in spleen extracts of mice, which received FLV suspensions preincubated with these compounds. Studies are now in progress to evaluate the leukemogenic activity of cell-free spleen extracts, prepared from mice inoculated with pretreated suspensions. Wu etal.63 have carried out such studies with RLV and rifamycin derivatives. They reported that the inoculation of mice with inocula from mice infected with RLV pretreated with AF-ABDP and AF/DNF1 did not cause splenomegaly. 

NkpSO, 44 46 IgSF tumor antigens viral activation... 

Interferons, IFN s belong to a group of cytokines of Mr in the range of 15.000 to 30.000. There are three types of interferons, INF-a, INF-/3 and INF-y. They are released by cells on exposure to inducing agents, such as viruses. A special property of the INF s is their anti-viral activity. 

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