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. 1988 May;85(10):3304–3308. doi: 10.1073/pnas.85.10.3304

Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.

J Badger 1, I Minor 1, M J Kremer 1, M A Oliveira 1, T J Smith 1, J P Griffith 1, D M Guerin 1, S Krishnaswamy 1, M Luo 1, M G Rossmann 1, et al.
PMCID: PMC280197  PMID: 2835768

Abstract

The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold E., Erickson J. W., Fout G. S., Frankenberger E. A., Hecht H. J., Luo M., Rossman M. G., Rueckert R. R. Virion orientation in cubic crystals of the human common cold virus HRV14. J Mol Biol. 1984 Aug 15;177(3):417–430. doi: 10.1016/0022-2836(84)90293-6. [DOI] [PubMed] [Google Scholar]
  2. Diana G. D., McKinlay M. A., Otto M. J., Akullian V., Oglesby C. [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating. J Med Chem. 1985 Dec;28(12):1906–1910. doi: 10.1021/jm00150a025. [DOI] [PubMed] [Google Scholar]
  3. Fox M. P., Otto M. J., McKinlay M. A. Prevention of rhinovirus and poliovirus uncoating by WIN 51711, a new antiviral drug. Antimicrob Agents Chemother. 1986 Jul;30(1):110–116. doi: 10.1128/aac.30.1.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  5. Lonberg-Holm K., Gosser L. B., Kauer J. C. Early alteration of poliovirus in infected cells and its specific inhibition. J Gen Virol. 1975 Jun;27(3):329–342. doi: 10.1099/0022-1317-27-3-329. [DOI] [PubMed] [Google Scholar]
  6. Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossmann M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  7. Ninomiya Y., Ohsawa C., Aoyama M., Umeda I., Suhara Y., Ishitsuka H. Antivirus agent, Ro 09-0410, binds to rhinovirus specifically and stabilizes the virus conformation. Virology. 1984 Apr 30;134(2):269–276. doi: 10.1016/0042-6822(84)90296-4. [DOI] [PubMed] [Google Scholar]
  8. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  9. Sherry B., Rueckert R. Evidence for at least two dominant neutralization antigens on human rhinovirus 14. J Virol. 1985 Jan;53(1):137–143. doi: 10.1128/jvi.53.1.137-143.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Smith T. J., Kremer M. J., Luo M., Vriend G., Arnold E., Kamer G., Rossmann M. G., McKinlay M. A., Diana G. D., Otto M. J. The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science. 1986 Sep 19;233(4770):1286–1293. doi: 10.1126/science.3018924. [DOI] [PubMed] [Google Scholar]

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