The long term objective is to carry out rational development of novel anti-AIDS drugs with high potency, low toxicity, and broad clinical applicability. We have discovered several new anti-HIV agents from distinct and unrelated plant species. Some of these are proteins, whereas others are organic polycyclic compounds. These agents exhibit dose-dependent inhibition of cell free HIV-1 infection and replications measured by: a) quantitative focal syncytium formation on CEM-ss monolayers, b) viral core protein p24 expression, and c) viral-associated reverse transcriptase activity in HIV infected H9 cells. We wish to study the structure-function relationship of these anti-HIV compounds so as to enable the rational design of safer and more effective analogues of anti-AIDS drugs. Peptide sequences and conformational requirements responsible for the anti-AIDS activities and cytotoxicity would be mapped. This may make possible the design of specific peptide fragments which may be useful as anti-HIV drugs with less immuno-genicity and improved pharmacokinetic properties (gut stability, biologic half-life, etc.) than their parent proteins. These sequences may then be further modified by targeted design to modulate and enhance their bioactive properties. We would also study the molecular mechanisms of the anti-HIV activity of these compounds so as to learn new strategies for the prevention and treatment of AIDS. A combination of biochemical, cellular, histochemical, and molecular methods will be used to conduct these studies. If the basis of the anti-HIV activity of these compounds lies in selective interactive or uptake, these may be of use in engineering the delivery of these and other drugs for patient treatment. If the basis of their action lies in a fundamental biochemical difference between HIV-infected cells and normal cells, this difference may be investigated and exploited in new interventions of AIDS.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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AIDS and Related Research Study Section 4 (ARRD)
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New York University
Schools of Medicine
New York
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Lee-Huang, Sylvia; Huang, Philip Lin; Huang, Paul Lee (2014) Live-cell real-time imaging of mitochondria in HIV-1-infected cells. AIDS Res Hum Retroviruses 30:1025-6
Li, Hui-Guang; Huang, Philip L; Zhang, Dawei et al. (2010) A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase--structural and modeling insight into its functions. Biochem Biophys Res Commun 391:340-5
Lee-Huang, Sylvia; Maiorov, Vladimir; Huang, Philip L et al. (2005) Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry 44:4648-55
Lee-Huang, S; Huang, P L; Sun, Y et al. (2000) Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30. Anticancer Res 20:653-9
Wang, Y X; Jacob, J; Wingfield, P T et al. (2000) Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP. Protein Sci 9:138-44
Wang, Y X; Neamati, N; Jacob, J et al. (1999) Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 99:433-42
Schreiber, C A; Wan, L; Sun, Y et al. (1999) The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertil Steril 72:686-90
Huang, P L; Sun, Y; Chen, H C et al. (1999) Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active. Biochem Biophys Res Commun 262:615-23
Bourinbaiar, A S; Lee-Huang, S (1996) The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus in vitro. Biochem Biophys Res Commun 219:923-9
Bourinbaiar, A S; Lee-Huang, S (1995) Acrosin inhibitor, 4'-acetamidophenyl 4-guanidinobenzoate, an experimental vaginal contraceptive with anti-HIV activity. Contraception 51:319-22

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