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Research on Hepatitis C Virus inhibitors has dramatically increased during the past few years. Actually, several classes of anti-HCV drugs, including NS3/4A protease inhibitors, NS5B polymerase inhibitors, NS4B protein to RNA binding inhibitors, and multifunctional viral protein NS5A inhibitors, are in different stages of development. The RNA dependent HCV polymerase is considered an irreplaceable target for future HCV therapy on account of a high degree of conservation across the six HCV genotypes, and agents targeting the active site, such as ribonucleoside analogs, may be particularly advantageous having a high barrier to resistance. The purpose of this review is to present highlights of recent developments in the synthesis of anti-HCV ribonucleosides and to discuss the limitations posed by resistance and drug toxicity.

Eaton, Monroe D. (Harvard Medical School, Boston, Mass.), Ann E. Farnham, Jeana D. Levinthal, and Anthony R. Scala . Cytopathic effect of the atypical pneumonia organism in cultures of human tissue. J. Bacteriol. 84: 1330–1337. 1962.—Three strains of the atypical pneumonia agent were adapted to grow in continuous cell cultures of human amnion or human embryonic lung, with production of initial increased acidity followed by destruction of the cells. Evidence is presented that cytopathic effects of the organism were associated with intracellular growth and formation of microcolonies. Clumps of organisms stained specifically with fluorescein-labeled antibody, and showed distinctive tinctorial reactions with the May Grünwald-Giemsa stain. The cytopathic effect was prevented by fresh serum from a rabbit immunized with an egg-passage strain of the atypical pneumonia agent. Heating the immune serum to 56 C for 30 min abolished the neutralizing effect. The significance of heat-labile serum constituents in killing or inhibition of mycoplasma is discussed.

Allergic encephalomyelitis (AE) , induced in rats and other animals by injection of