Inhibitors and Probes of HIV-1 Cell Fusion

Bewley, Carole

Abstract

The Natural Products Chemistry Section, LBC, NIDDK has several ongoing projects whose long term aim is to identify and design inhibitors and probes of HIV-1 Envelope-mediated cell fusion. These include the design and development of new gp41-derived peptides and proteins that have dual functions as inhibitors and immunogens, discovery and high resolution structural characterization of new carbohydrate binding proteins that potently inhibit HIV-1 Entry through carbohydrate-mediated interactions with gp120/gp41, discovery of natural product inhibitors of HIV-1 fusion, and structural and mechanistic studies of HIV-1 Envelope - coreceptor interactions.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIADK032103-13
• Application #: 8553437
• Support Year: 13
• Fiscal Year: 2012
• Total Cost: $827,494

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases

Publications

Lusvarghi, Sabrina; Ghirlando, Rodolfo; Davison, Jack R et al. (2018) Chemical and Biophysical Approaches for Complete Characterization of Lectin-Carbohydrate Interactions. Methods Enzymol 598:3-35

Zhou, Tongqing; Zheng, Anqi; Baxa, Ulrich et al. (2018) A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Immunity 48:500-513.e6

Shahzad-Ul-Hussan, Syed; Sastry, Mallika; Lemmin, Thomas et al. (2017) Insights from NMR Spectroscopy into the Conformational Properties of Man-9 and Its Recognition by Two HIV Binding Proteins. Chembiochem 18:764-771

Bobyk, Kostyantyn D; Mandadapu, Sivakoteswara R; Lohith, Katheryn et al. (2017) Design of HIV Coreceptor Derived Peptides That Inhibit Viral Entry at Submicromolar Concentrations. Mol Pharm 14:2681-2689

Lusvarghi, Sabrina; Bewley, Carole A (2016) Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential. Viruses 8:

Lusvarghi, Sabrina; Lohith, Katheryn; Morin-Leisk, Jeanne et al. (2016) Binding Site Geometry and Subdomain Valency Control Effects of Neutralizing Lectins on HIV-1 Viral Particles. ACS Infect Dis 2:882-891

Mason, Rosemarie D; Welles, Hugh C; Adams, Cameron et al. (2016) Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog 12:e1005537

Dogo-Isonagie, Cajetan; Lee, Su-Lin; Lohith, Katheryn et al. (2016) Design and synthesis of small molecule-sulfotyrosine mimetics that inhibit HIV-1 entry. Bioorg Med Chem 24:1718-28

Stewart-Jones, Guillaume B E; Soto, Cinque; Lemmin, Thomas et al. (2016) Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell 165:813-26

Mason, Rosemarie D; Welles, Hugh C; Adams, Cameron et al. (2016) Correction: Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog 12:e1005674