The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing
Open accessAbstract
New HIV therapies are urgently needed to address the growing problem of drug resistance. In this article, we characterize the anti-HIV drug candidate 3- O -(3′,3′-dimethylsuccinyl) betulinic acid (PA-457). We show that PA-457 potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). We find that virions from PA-457-treated cultures are noninfectious and exhibit an aberrant particle morphology characterized by a spherical, acentric core and a crescent-shaped, electron-dense shell lying just inside the viral membrane. To identify the determinants of compound activity we selected for PA-457-resistant virus in vitro . Consistent with the effect on Gag processing, we found that mutations conferring resistance to PA-457 map to the p25 to p24 cleavage site. PA-457 represents a unique class of anti-HIV compounds termed maturation inhibitors that exploit a previously unidentified viral target, providing additional opportunities for HIV drug discovery.
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Cites
Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding
Garrus, J. E., von Schwedler, U. K., Pornillos, O. W., Morham, S. G., Zavitz, K. H., Wang, H. E., Wettstein, D. A., Stray, K. M., Côté, M., Rich, R. L., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00506-2 · Cited by 1,369
HIV-1 Gag proteins: diverse functions in the virus life cycle
Freed, E. O. (1998) · Virology · doi:10.1006/viro.1998.9398 · Cited by 717
Self-citationMartin-Serrano, J., Zang, T., & Bieniasz, P. D. (2001) · Nature Medicine · doi:10.1038/nm1201-1313 · Cited by 710
Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release
Göttlinger, H. G., Dorfman, T., Sodroski, J. G., & Haseltine, W. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.8.3195 · Cited by 647
Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55 Gag
VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J., & Carter, C. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131059198 · Cited by 584
Wiegers, K., Rutter, G., Kottler, H., Tessmer, U., Hohenberg, H., & Kräusslich, H.-G. (1998) · Journal of Virology · doi:10.1128/jvi.72.4.2846-2854.1998 · Cited by 336
Demirov, D. G., Orenstein, J. M., & Freed, E. O. (2002) · Journal of Virology · doi:10.1128/jvi.76.1.105-117.2002 · Cited by 201
Self-citationAccola, M. A., Höglund, S., & Göttlinger, H. G. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2072-2078.1998 · Cited by 196
Cited by
HIV-1 assembly, release and maturation
Freed, E. O. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3490 · Cited by 654
Self-citationElectron cryotomography of immature HIV‐1 virions reveals the structure of the CA and SP1 Gag shells
Wright, E. R., Schooler, J. B., Ding, H. J., Kieffer, C., Fillmore, C., Sundquist, W. I., & Jensen, G. J. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601664 · Cited by 325
Human immunodeficiency virus type 1 assembly, release, and maturation
Adamson, C. S., & Freed, E. O. (2007) · Advances in Pharmacology · doi:10.1016/s1054-3589(07)55010-6 · Cited by 179
Self-citationRetroviral proteases and their roles in virion maturation
Konvalinka, J., Kräusslich, H.-G., & Müller, B. (2015) · Virology · doi:10.1016/j.virol.2015.03.021 · Cited by 148
Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography
de Marco, A., Müller, B., Glass, B., Riches, J. D., Kräusslich, H.-G., & Briggs, J. A. G. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001215 · Cited by 114
Metadata
- Authors
- Li, F., Goila-Gaur, R., Salzwedel, K., Kilgore, N. R., Reddick, M., Matallana, C., Castillo, A., Zoumplis, D., Martin, D. E., Orenstein, J. M., Allaway, G. P., Freed, E. O., & Wild, C. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-10-22
- Volume
- 100
- Issue
- 23
- Pages
- 13555-13560
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2132762790
- Cited by
- 426
- References
- 8
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Li, F., Goila-Gaur, R., Salzwedel, K., Kilgore, N. R., Reddick, M., Matallana, C., Castillo, A., Zoumplis, D., Martin, D. E., Orenstein, J. M., Allaway, G. P., Freed, E. O., & Wild, C. T. (2003). PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2234683100
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
