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BACKGROUND Group B coxsackieviruses (CVBs) are etiologic agents of a number of human diseases that range in severity from asymptomatic to lethal infections. They are small, single-stranded RNA icosahedral viruses that belong to the enterovirus genus of the picornavirus family. Structural studies were initiated in light of the information available on the(More)
The structure of human rhinovirus 1A (HRV1A) has been determined to 3.2 A resolution using phase refinement and extension by symmetry averaging starting with phases at 5 A resolution calculated from the known human rhinovirus 14 (HRV14) structure. The polypeptide backbone structures of HRV1A and HRV14 are similar, but the exposed surfaces are rather(More)
A series of eight antiviral compounds complexed with human rhinovirus 14 (HRV-14) were previously shown to displace segments of polypeptide chains in the floor of the "canyon" by as much as 0.45 nm in C-alpha positions from the native conformation (J. Badger, I. Minor, M. J. Kremer, M. A. Oliveira, T. J. Smith, J. P. Griffith, D. M. A. Guerin, S.(More)
Macrophages harvested from the peritoneal cavities of mice of several strains were permissive to infection with murine cytomegalovirus (MCMV). Macrophages from six mouse strains released equivalent amounts of plaque-forming virus into the culture fluids and cells from mouse strains scored similarly in numbers of infectious centres. Twenty to 50% of the(More)
Six commonly used strains of lymphocytic choriomeningitis virus (LCMV) [Armstrong (Arm) CA 1371, Arm E-350, WE, UBC, Traub and Pasteur C1PV 76001] were examined for distinctive genetic and biological properties. Agarose gel electrophoresis yielded no detectable differences among the L or S RNAs of these six strains. The RNase T1 fingerprint patterns of LCMV(More)
Spontaneous mutants of human rhinovirus 14 resistant to WIN 52084, an antiviral compound that inhibits attachment to cells, were isolated by selecting plaques that developed when wild-type virus was plated in the presence of high (2 micrograms/ml) or low (0.1 to 0.4 micrograms/ml) concentrations of the compound. Two classes of drug resistance were observed:(More)
Several modifications of the oxazoline ring of WIN 54954, a broad spectrum antipicornavirus compound, have been prepared in order to address the acid lability and metabolic instability of this compound. We have previously shown that the oxadiazole analogue 3 displayed comparable activity against a variety of rhinoviruses and appeared to be stable to acid. A(More)
Crystallographic studies of human rhinovirus 14 (HRV14) crystals soaked with fragments of antiviral WIN compounds, at high concentrations (82-200 micrograms/ml), show the compounds bind into the hydrophobic beta-barrel (WIN pocket) of VP1. Two of these short compounds (5-[3,5-dimethyl-4-hydroxyphenyl]-2-methyltetrazole and phenol oxazoline) cause(More)
The binding affinities (Kds) and the rates of association and dissociation of members of a chemical class of antiviral compounds at their active sites in human rhinovirus type 14 (HRV-14) were determined. On the basis of analysis by LIGAND, a nonlinear curve-fitting program, of saturation binding experiments with HRV-14, the Kds for Win 52084, Win 56590,(More)