92 resultados para nucleoside reverse transcriptase inhibitor


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Pós-graduação em Agronomia (Proteção de Plantas) - FCA

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Pós-graduação em Biologia Geral e Aplicada - IBB

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Pós-graduação em Medicina Veterinária - FMVZ

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Telomeres are the physical ends of eukaryotic linear chromosomes. Telomeres form special structures that cap chromosome ends to prevent degradation by nucleolytic attack and to distinguish chromosome termini from DNA double-strand breaks. With few exceptions, telomeres are composed primarily of repetitive DNA associated with proteins that interact specifically with double- or single-stranded telomeric DNA or with each other, forming highly ordered and dynamic complexes involved in telomere maintenance and length regulation. In proliferative cells and unicellular organisms, telomeric DNA is replicated by the actions of telomerase, a specialized reverse transcriptase. In the absence of telomerase, some cells employ a recombination-based DNA replication pathway known as alternative lengthening of telomeres. However, mammalian somatic cells that naturally lack telomerase activity show telomere shortening with increasing age leading to cell cycle arrest and senescence. In another way, mutations or deletions of telomerase components can lead to inherited genetic disorders, and the depletion of telomeric proteins can elicit the action of distinct kinases-dependent DNA damage response, culminating in chromosomal abnormalities that are incompatible with life. In addition to the intricate network formed by the interrelationships among telomeric proteins, long noncoding RNAs that arise from subtelomeric regions, named telomeric repeat-containing RNA, are also implicated in telomerase regulation and telomere maintenance. The goal for the next years is to increase our knowledge about the mechanisms that regulate telomere homeostasis and the means by which their absence or defect can elicit telomere dysfunction, which generally results in gross genomic instability and genetic diseases.

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Respiratory syncytial virus is the major cause of acute lower respiratory tract illness in infants and young children. Because there is currently no licensed vaccine for RSV, there is a substantial interest in the identification and development of RSV specific inhibitory agents. There are clinical evidences that glycosaminoglycans (GAGs) are potential inhibitors of viral infection. In this study, the performance of two GAGs (heparin and dextran sulfate) were compared for their antiviral and virucidal activities on RSV. Analysis was performed using an in vitro infection model where, previously to infection, Hep-2 cells or RSV were incubated with heparin or dextran sulfate. The presence of viral particles was analyzed by Reverse Transcriptase-Polimerase Chain Reaction (RT-PCR) and indirect immunofluorescence assays (IFA). The results showed that viral infection was more efficiently inhibited when Hep-2 cells were pre-incubated with heparin or, when viral particles were pre-incubated with dextran sulfate. Our study suggest that, in the absence of cellular death, heparin and dextran sulfate reduce RSV infection by different mechanisms, antiviral and virucidal ones, respectively. These data contribute for recent medical, microbiology and biochemical studies which suggest that the use of antiviral and virucidal compounds as more effective treatment to control virus infections.

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