DOI: 10.1073/pnas.95.12.6774. Antiviral agent blocks breathing of the common cold virus

Antiviral agent blocks breathing of the common cold virus

10.1073/pnas.95.12.6774

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

A dynamic capsid is critical to the events that shape the viral life cycle; events such as cell attachment, cell entry, and nucleic acid release demand a highly mobile viral surface. Protein mass mapping of the common cold virus, human rhinovirus 14 (HRV14), revealed both viral structural dynamics and the inhibition of such dynamics with an antiviral agent, WIN 52084. Viral capsid digestion fragments resulting from proteolytic time-course experiments provided structural information in good agreement with the HRV14 three-dimensional crystal structure. As expected, initial digestion fragments included peptides from the capsid protein VP1. This observation was expected because VP1 is the most external viral protein. Initial digestion fragments also included peptides belonging to VP4, the most internal capsid protein. The mass spectral results together with x-ray crystallography data provide information consistent with a “breathing” model of the viral capsid. Whereas the crystal structure of HRV14 shows VP4 to be the most internal capsid protein, mass spectral results show VP4 fragments to be among the first digestion fragments observed. Taken together this information demonstrates that VP4 is transiently exposed to the viral surface via viral breathing. Comparative digests of HRV14 in the presence and absence of WIN 52084 revealed a dramatic inhibition of digestion. These results indicate that the binding of the antiviral agent not only causes local conformational changes in the drug binding pocket but actually stabilizes the entire viral capsid against enzymatic degradation. Viral capsid mass mapping provides a fast and sensitive method for probing viral structural dynamics as well as providing a means for investigating antiviral drug efficacy.

Bibliography

Lewis, J. K., Bothner, B., Smith, T. J., & Siuzdak, G. (1998). Antiviral agent blocks breathing of the common cold virus. Proceedings of the National Academy of Sciences, 95(12), 6774â6778.

Authors 4

J. Kathleen Lewis (first)
Brian Bothner (additional)
Thomas J. Smith (additional)
Gary Siuzdak (additional)

References 25 Referenced 224

R R Rueckert Picornaviridae and Their Replication (Raven, New York), pp. 609–654 (1996). / Picornaviridae and Their Replication by Rueckert R R (1996)
Rossmann M. G. Smith T. J. & Rueckert R. R. (1993) Structure Introductory Issue xxiv–xxv.
10.1002/pro.5560040607
10.1021/ja960752m
10.1074/jbc.273.2.673
10.1073/pnas.80.4.931
10.1128/jvi.68.6.3965-3970.1994
10.1038/317145a0
10.1073/pnas.90.2.507
10.1126/science.3018924
10.1128/jvi.63.5.2002-2007.1989
10.1099/0022-1317-72-9-2153
10.1128/AAC.30.1.110
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C N Hiremath, D J Filman, R A Grant, J M Hogle Acta Crystallogr D53, 558–570 (1997). / Acta Crystallogr by Hiremath C N (1997)
10.1128/jvi.68.12.8193-8201.1994
10.1128/jvi.67.3.1246-1254.1993
10.1128/jvi.67.1.390-397.1993
W M Lee Dissertation (University of Wisconsin, Madison, 1992). / Dissertation by Lee W M (1992)
10.1038/383350a0
M Chow, R Basavappa, J Hogle Structural Biology of Viruses, eds W Chiu, R M Burnett, R L Garcea (Oxford, New York), pp. 157–186 (1997). / Structural Biology of Viruses by Chow M (1997)
D C Pevear, G D Diana, M A McKinlay Semin Virol 2, 41–55 (1992). / Semin Virol by Pevear D C (1992)
10.1016/0022-2836(90)90076-X
10.1016/B978-012647471-8/50008-9
10.1016/0263-7855(94)00019-O

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:35 p.m.)
Indexed	1 week, 3 days ago (Aug. 19, 2025, 7 a.m.)
Issued	27 years, 2 months ago (June 9, 1998)
Published	27 years, 2 months ago (June 9, 1998)
Published Online	27 years, 2 months ago (June 9, 1998)
Published Print	27 years, 2 months ago (June 9, 1998)

Funders 0

None

BibTeX

@article{Lewis_1998, title={Antiviral agent blocks breathing of the common cold virus}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.12.6774}, DOI={10.1073/pnas.95.12.6774}, number={12}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lewis, J. Kathleen and Bothner, Brian and Smith, Thomas J. and Siuzdak, Gary}, year={1998}, month=jun, pages={6774–6778} }

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