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.

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2013
Total Cost
$794,394
Indirect Cost
City
State
Country
Zip Code
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
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
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
Sastry, Mallika; Bewley, Carole A; Kwong, Peter D (2015) Effective isotope labeling of proteins in a mammalian expression system. Methods Enzymol 565:289-307
Acharya, Priyamvada; Lusvarghi, Sabrina; Bewley, Carole A et al. (2015) HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets 19:765-83

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