Measles Research Today is a free monthly online journal that collates and summarizes the latest research about Measles, including details on german measles, symptoms, vaccine, treatment, rubella.

Potent Non-Nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase Complex.

Sun A, Yoon JJ, Yin Y, Prussia A, Yang Y, Min J, Plemper RK, Snyder JP

Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, Department of Pediatrics, Division of Pediatric Infectious Diseases, Emory Children's Center, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, Georgia 30322 asun2@emory.edu, jsnyder@emory.edu.

Measles virus (MV) is one of the most infectious pathogens known. In spite of the existence of a vaccine, approximately 350000 deaths/year result from MV or associated complications. Antimeasles compounds could conceivably diminish these statistics and provide a therapy that complements vaccine treatment. We recently described a high-throughput screening hit compound 1 (16677) against MV-infected cells with the capacity to eliminate viral reproduction at 250 nM by inhibiting the action of the virus's RNA-dependent RNA polymerase complex (RdRp). The compound, 1-methyl-3-(trifluoromethyl)- N-[4-sulfonylphenyl]-1 H-pyrazole-5-carboxamide, 1 carries a critical CF 3 moiety on the 1,2-pyrazole ring. Elaborating on the preliminary structure-activity (SAR) study, the present work presents the synthesis and SAR of a much broader range of low nanomolar nonpeptidic MV inhibitors and speculates on the role of the CF 3 functionality.

Published 4 July 2008 in J Med Chem, 51(13): 3731-3741.
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Articles on Measles published 4 July 2008:

Immunogenicity and Safety Assessments After One and Two Doses of a Refrigerator-Stable Tetravalent Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children During the Second Year of Life.   Pediatr Infect Dis J.

BACKGROUND:: Measles, mumps, and rubella (MMR) and varicella (V) vaccines are often coadministered at 1 clinic visit. This study (104389/NCT00127023) was undertaken to assess the immunogenicity and safety of a new refrigerator-stable tetravalent MMRV vaccine after 1 dose and after 2 doses administered during the second year of life. METHODS:: Nine hundred seventy healthy children aged 10-21 months received 2 doses of MMRV vaccine (Priorix-Tetra; GlaxoSmithKline Biologicals, Rixensart, Belgium) ... [Abstract] [Full-text]

Vaccine immunogenetics: Bedside to bench to population.   Vaccine.

The immunogenetic basis for variations in immune response to vaccines in humans remains largely unknown. Many factors can contribute to the heterogeneity of vaccine-induced immune responses, including polymorphisms of immune response genes. It is important to identify those genes involved directly or indirectly in the generation of the immune response to vaccines. Our previous work with measles reveals the impact of immune response gene polymorphisms on measles vaccine-induced humoral and ... [Abstract] [Full-text]

Articles on Measles published 3 July 2008:

Measles virus breaks through epithelial cell barriers to achieve transmission.   J Clin Invest, 118(7): 2386-9.

Measles is a highly contagious disease that causes immunosuppression in patients. Measles virus infection has been thought to begin in the respiratory epithelium and then spread to lymphoid tissue. In this issue of the JCI, Leonard et al. provide data to suggest an alternative model of measles virus pathogenesis (see the related article beginning on page 2448). In human primary epithelial cells and rhesus monkeys in vivo, the authors show that initial infection of respiratory epithelium is not ... [Abstract] [Full-text]

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed.   J Clin Invest, 118(7): 2448-2458.

The current model of measles virus (MV) pathogenesis implies that apical infection of airway epithelial cells precedes systemic spread. An alternative model suggests that primarily infected lymphatic cells carry MV to the basolateral surface of epithelial cells, supporting MV shedding into the airway lumen and contagion. This model predicts that a mutant MV, unable to enter cells through the unidentified epithelial cell receptor (EpR), would remain virulent but not be shed. To test this model, ... [Abstract] [Full-text]

Articles on Measles published 1 July 2008:

Heat shock protein inhibitors increase the efficacy of measles virotherapy.   Gene Ther, 15(14): 1024-34.

Oncolytic measles virus strains have activity against multiple tumor types and are currently in phase I clinical testing. Induction of the heat shock protein 70 (HSP70) constitutes one of the earliest changes in cellular gene expression following infection with RNA viruses including measles virus, and HSP70 upregulation induced by heat shock has been shown to result in increased measles virus cytotoxicity. HSP90 inhibitors such as geldanamycin (GA) or 17-allylaminogeldanamycin result in ... [Abstract] [Full-text]

Articles on Measles published 30 June 2008:

Thymus Size at 6 Months of Age and Subsequent Child Mortality.   J Pediatr.

OBJECTIVE: To examine determinants of thymus size at age 6 months and investigate whether thymus size at this age is a determinant of subsequent mortality. STUDY DESIGN: Thymus size was measured by transsternal sonography in 923 6-month-old children participating in a measles vaccination trial in Guinea-Bissau. RESULTS: Thymus size was strongly associated with anthropometric measurements. Boys had larger thymuses than girls, controlling for anthropometry. Crying during sonography made the ... [Abstract] [Full-text]

ELISA underestimates measles antibody seroprevalence in US military recruits.   Vaccine.

The prevalence of antibodies to measles, mumps, and rubella in US military recruits is of importance to public health leaders. We performed ELISA testing using a commercially available product on samples from 537 recruits obtained in 1998, of which 437 were positive (81%). We then performed a validation study in a subsample of the population using plaque reduction neutralization (PRN) to assess misclassification error. This resulted in a corrected estimate of the prevalence of immunity to ... [Abstract] [Full-text]

Measles serological survey in the Italian population: Interpretation of results using mixture model.   Vaccine.

In 2003-2004, a national measles seroprevalence study was conducted in Italy and data were analysed by using both commercial ELISA cut-off, and by applying a mixture model. Results of the two methods were compared and interpreted in the light of measles incidence, vaccination coverage and previous seroprevalence data. Seroprevalence rates observed in 2004 were similar to those observed in a previous study conducted in 1996 for children up to 9 years of age, while they were significantly lower ... [Abstract] [Full-text]

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