Virus Replication

A rather distantly related analogue incorporating a 3-di-carbonyl moiety as a bioisosteric replacement for a carboxyl, aril done (55), blocks the uncoating of polio virus and herpes simplex virus type I and thus inhibits infection of cells and l.he early stages of virus replication. Thus effective therapy would require careful timing as it does with amantidine. 

Virus Replication Inhibitors and Stimulators from Plant Sources... 

Extracts from 152 plant species, representing 46 different families, were screened for effects on tobacco mosaic virus (TMV) replication in cucumber cotyledons. Twenty species have shown enough activity to warrant further study. Several members of the Caprifoliaceae family increased virus replication. An extract of Lonicera involucrata enlarged the virus lesions in local lesion hosts and produced a thirty fold increase in virus titer, but had no effect on virus replication in systemic hosts. The active material appears to affect the virus defense mechanism of local lesion hosts. An extract of common geranium is an active virus inhibitor. It inactivates TMV and TMV-RNA (ribonucleic acid) in vitro by forming non-infectious complexes. In vivo, it also inhibited starch lesion formation in cucumber cotyledons incited by TMV infection. 

J he abundance of organic materials that occur in the plant kingdom offer an opportunity for searching for specific compounds interfering with virus replication in plants. It is hoped that such compounds, if discovered, could be used efficiently for virus control and also serve as tools for our understanding of the complex virus-host system. 

Lesion formation represents a host response to virus infection. Factors preventing the formation of starch lesions incited by the virus do not necessarily mean that virus replication is inhibited at the same time. Therefore, the total virus titer in cotyledon samples treated with different concentrations of tannic acid was determined (Figure... 

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J et al. (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299 893-896 Ehon GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxy ethoxy methyl) guanine, Proc Natl Acad Sci USA 74 5716-5720... 

Stuyver LJ, McBrayer TR, Tharnish PM, Clark J, Hollecker L, Lostia S, Nachman T, Grier J, Bennett MA, Xie MY, Schinazi RF, Morrey JD, Inlander JL, Furman PA, Otto MJ (2006a) Inhibition of hepatitis C replicon RNA synthesis by beta-D-2 -deoxy-2 -fluoro-2 -C-methylcytidine a specific inhibitor of hepatitis C virus replication, Antivir Chem Chemother 17 79-87... 

DJ, Flores OA (2003) Characterization of resistance to non-obligate chain-terminating ribonu-cleoside analogs that inhibit hepatitis C virus replication in vitro. J Biol Chem 278 49164-49170... 

A major limitation in the development of anti-HCV compounds was the lack of a virus replication system. This was finally overcome with the development of a novel replicon system that directed persistent replication in a cell culture format (Lohmann et al. 1999). Using such a system, it was possible to demonstrate antiviral activity of an NS3/4A inhibitor in a cell culture assay, and demonstrate potency on par with treatment with interferon-a (Pause et al. 2003). 

Palese P, Schulman JL, Bodo G, Meindl P (1974a) Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-V-trifluoroacetylneuraminic acid (FANA), Virology 59 490 98... 

Ryan DM, Ticehurst J, Dempsey M, Penn CR (1994) Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-iV-acetylneuraminic add) is consistent with extracellular actiivity of viral neuraminidase (sialidase), Antimicrob Agents Chemother 10 2270-2275... 

Wild C, Oas T, McDanal C, Bolognesi D, Matthews T (1992) A synthetic peptide inhibitor of human immunodeficiency virus replication correlation between solution structure and viral inhibition, Proc Natl Acad Sci USA 89 10537-10541... 

Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C, Bowman K, Shaffer CS, Pohsky BA, Zinnen S (2005a) Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41 1349-1356... 

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