Journal article
Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation
The Journal of biological chemistry, v 290(1), pp 529-543
02 Jan 2015
PMID: 25371202
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally.
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Details
- Title
- Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation
- Creators
- Arangassery Rosemary Bastian - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Aakansha Nangarlia - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Lauren D Bailey - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Andrew Holmes - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102R Venkat Kalyana Sundaram - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Charles Ang - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Diogo R M Moreira - the Fundação Oswaldo Cruz, Centro de Pesquisas Goncalo Moniz, Salvador-BA 40296-710, BrazilKevin Freedman - the Department of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania 19104, andCaitlin Duffy - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Mark Contarino - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102Cameron Abrams - the Department of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania 19104, andMichael Root - the Department of Biochemistry and Molecular Biology, Jefferson University, Philadelphia, Pennsylvania 19107Irwin Chaiken - From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, Irwin.chaiken@drexelmed.edu
- Publication Details
- The Journal of biological chemistry, v 290(1), pp 529-543
- Publisher
- ASBMB Publications / Elsevier; United States
- Grant note
- P01 GM056550 / NIGMS NIH HHS R01 GM111029 / NIGMS NIH HHS R01GM11029 / NIGMS NIH HHS P30 CA056036 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Thomas R. Kline School of Law; Chemical and Biological Engineering
- Web of Science ID
- WOS:000347231200046
- Scopus ID
- 2-s2.0-84920545972
- Other Identifier
- 991014878005304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology