Viruses modification

The whole virus modification with the thiuram disulfides. HIV-1 (MN) (equivalent of 1 mg p24 CA) in 20 ml was treated at 37 C with 50 mM test compoimds for 1 h in sodium phosphate buffer, pH 7. Samples were centrifuged for 1 h at 17,000 g at 4 °C to pellet the virus and remove the drug. Samples for electrophoresis were run under non-reducing conditions. The gels (4-20%) were supplied by NOVEX (San Diego, California). Then proteins were transferred onto PVDF membranes (Towbin et. al., 1979), stained with 0.5% (w/v) Ponceau S and detected by... 

Applications that use intramers include inhibition of Ihe spread of a virus by inhibiting the transcription factor associated with that virus. Modifications to the aptamer that need to be made in order to turn it into an appropriate intramer will depend on the cell type of the target. In some cells, the aptamer can be directly cultured with the cells while experiencing very little deterioration as a result of the nuclease of the cell. 

Apart from the applications in synthesizing drug molecules with a triazole linkage, azide-alkyne cycloaddition reactions have also been used for various biological applications such as site-specific protein/viruses modifications and functionalization of cell surfaces. Use of transition-metal-catalyzed reactions for... 

The original Central Dogma of molecular biology (left) and its modification in light of the discovery of viruses (right). 

Despite these intense efforts to test different chemical modifications, there is so far little success in developing potent and safe antivirals. For hepatitis C virus (HCV), McHutchison et al. reported in vivo side effects of a 20-nucleotide PS-modified ohgonucleotide (ISIS-14803) (McHutchison et al. 2006). In a test group of 28 patients, only 3 patients responded to the treatment by a reduction in the HCV viral load. The researchers concluded that further studies are needed to evaluate this novel agent and its side effects. Previously, ISIS Pharmaceuticals reported a 3.8 log reduction in plasma virus in patients with chronic HCV infection, using ISIS-14803 (www.isispharm.com). 

Yi L, Shi J, Gao S et al (2009) Sulfonium alkylation followed by click chemistry for facile surface modification of proteins and tobacco mosaic virus. Tetrahedron Lett 50 759-762... 

Schlick TL, Ding Z, Kovacs EW, Francis MB (2005) Dual-surface modification of the tobacco mosaic virus. J Am Chem Soc 127 3718-3723... 

Virus restriction and modification by the host We have already seen that one form of host resistance to virus arises when there is no receptor site on the cell surface to which the virus can attach. Another and more specific kind of host resistance involves destruction of the viral nucleic acid after it has been injected. This destruction is brought about by host enzymes that cleave the viral DNA at one or several places, thus preventing its replication. This phenomenon is called restriction, and is part of a general host mechanism to prevent the invasion of foreign nucleic acid. 

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