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

J. Badger, I. Minor, M. J. Kremer, M. A. Oliveira, T. J. Smith, J. P. Griffith, D. M.A. Guerin, S. Krishnaswamy, M. Luo, M. G. Rossmann, M. A. McKinlay, G. D. Diana, F. J. Dutko, M. Fancher, R. R. Rueckert, B. A. Heinz

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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 β-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.

Original languageEnglish (US)
Pages (from-to)3304-3308
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number10
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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Badger, J., Minor, I., Kremer, M. J., Oliveira, M. A., Smith, T. J., Griffith, J. P., Guerin, D. M. A., Krishnaswamy, S., Luo, M., Rossmann, M. G., McKinlay, M. A., Diana, G. D., Dutko, F. J., Fancher, M., Rueckert, R. R., & Heinz, B. A. (1988). Structural analysis of a series of antiviral agents complexed with human rhinovirus 14. Proceedings of the National Academy of Sciences of the United States of America, 85(10), 3304-3308. https://doi.org/10.1073/pnas.85.10.3304