The Site of Attachment in Human Rhinovirus 14 for Antiviral Agents That Inhibit Uncoating

Smith, Thomas J.; Kremer, Marcia J.; Luo, Ming; Vriend, Gerrit; Arnold, Edward; Kamer, Greg; Rossmann, Michael G.; McKinlay, Mark A.; Diana, Guy D.; Otto, Michael

doi:10.1126/science.3018924

Cited by 445 publications

(225 citation statements)

References 24 publications

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“…Direct evidence for involvement of the canyon in HRV-14 attachment to cells was obtained when appropriate mutagenesis was shown to give viruses with an altered affinity for the cell receptor (Colonno et al, 1988). In addition, drugs known to bind inside a hydrophobic pocket underneath the canyon, resulting in a distortion of the canyon floor, prevent attachment of this rhinovirus serotype (Smith et al, 1986;Pevear et al, 1989). A similar canyon is observed in the structures of poliovirus types 1 and 3 and Mengo virus and thus there is strong direct and comparative evidence that it is functionally active in a range of picornaviruses (Rossmann & Palmenberg, 1988).…”

Section: Capsid Proteinsmentioning

confidence: 77%

Structure, function and evolution of picornaviruses

Stanway

1990

Journal of General Virology

160

105

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Section: Capsid Proteinsmentioning

confidence: 77%

Structure, function and evolution of picornaviruses

Stanway

1990

Journal of General Virology

160

105

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“…Furthermore, the ΦX174 structure, in contrast to other icosahedral viruses, shows only little contact of the β-barrel fold with neighbouring subunits, as it essentially projects into the DNA core (Table 3). It has also been suggested 59,60 that the fold might be conserved to modulate viral stability by virtue of its hydrophobic interior.…”

Section: Evolutionmentioning

confidence: 99%

Atomic structure of single-stranded DNA bacteriophage ΦX174 and its functional implications

McKenna

Xia

Willingmann

et al. 1992

Nature

Self Cite

215

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The mechanism of DNA ejection, viral assembly and evolution are related to the structure of bacteriophage ΦX174. The F protein forms a T = 1 capsid whose major folding motif is the eightstranded antiparallel β barrel found in many other icosahedral viruses. Groups of 5 G proteins form 12 dominating spikes that enclose a hydrophilic channel containing some diffuse electron density. Each G protein is a tight β barrel with its strands running radially outwards and with a topology similar to that of the F protein. The 12 'pilot' H proteins per virion may be partially located in the putative ion channel. The small, basic J protein is associated with the DNA and is situated in an interior cleft of the F protein. Tentatively, there are three regions of partially ordered DNA structure, accounting for about 12% of the total genome.Bacteriophage ΦX174 is a small icosahedral virus that contains a single-stranded, closed circular DNA molecule with 5,386 nucleotide bases (for a recent review, see ref. 1). Of the 11 gene products, four (J, F, G and H) participate in the structure of the virion. There are 60 copies each of the J, F and G proteins and 12 copies of the H protein per virion [2][3][4] (Table 1). Electron microscopy of shadowed or negatively stained particles [5][6][7][8] , as well as a threedimensional reconstruction of frozen-hydrated virions (Fig. 1a), clearly show large spikes at the vertices of the icosahedral particles (N.H.O., T.S.B., P.W. and N.L.I., manuscript in preparation). These spikes are about 32 Å long and have a mean diameter of 70 Å. Edgell et al. 3 have shown that these spikes, which can be removed from the capsid with 4 M urea treatment, are composed of G and H proteins. Assuming all 12 spikes are identical, then each spike will contain five G and one H protein 2 . The capsid itself has an external diameter of roughly 260 Å, with a protein shell that is about 30 Å thick, and contains the F and J proteins as well as the single-stranded (ss) DNA. The phage recognizes a lipopolysaccharide (LPS) receptor on the outer cell membrane of Escherichia coli [8][9][10][11] . Host range mutants, which determine which strains of E. coli are infected by ΦX174, map into the F, G and H genes [12][13][14][15] The infectious virion has a relative molecular mass of 6.2 × 10 6 (M r 6,200K) (26% is DNA) 32 . Lysates of infected E. coli contain two components which can be separated by sedimentation through a sucrose gradient 32,33 . The fast band contains the infectious 114S particles whereas the slow band contains noninfectious, 70S particles 32,34,35 . The latter contains about 20% of the normal DNA content with all of the genome represented in the population of particles. Both types of particles can be crystallized into isomorphous monoclinic crystals with space group P2 1 , and cell dimensions a = 305.6, b = 360.8, c = 299.5 Å, β = 92.89° that diffract at least to 2.6-Å resolution 33 . The asymmetric unit of the crystal cell contains one complete particle. We report here the three-dimensional structure...

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“…This change of structure has also been observed in vitro upon incubation of virions at low pH or at 56 °C (Korant et al, 1972;Kowalski et al, 1989). Recently, several antiviral compounds have been synthesized which were shown to bind to a hydrophobic pocket in the viral capsid (Smith et al, 1986). For the members of the rhinovirus major receptor group, the effect of these compounds has been attributed to a displacement of the canyon floor, the putative receptor binding site, thus disturbing receptor recognition Rossmann et al, 1985;.…”

mentioning

confidence: 96%

Stabilization of human rhinovirus serotype 2 against pH-induced conformational change by antiviral compounds

Gruenberger

Pevear²,

Diana

et al. 1991

Journal of General Virology

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Four WIN compounds with anti-picornavirus activities were tested for their ability to stabilize human rhinovirus serotype 2 (HRV-2) against low pH-induced conformational changes in vitro, as determined by specific immunoprecipitation. These results were compared to the minimal inhibitory concentration (MIC) as measured in a plaque reduction assay. A direct relationship was observed between the concentration of the compound that prevented the low pH-induced conformational changes and the MIC, indicating that stabilization is an important element in the mode of action of these drugs against HRV-2.

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The Site of Attachment in Human Rhinovirus 14 for Antiviral Agents That Inhibit Uncoating

Cited by 445 publications

References 24 publications

Structure, function and evolution of picornaviruses

Structure, function and evolution of picornaviruses

Atomic structure of single-stranded DNA bacteriophage ΦX174 and its functional implications

Stabilization of human rhinovirus serotype 2 against pH-induced conformational change by antiviral compounds

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