PAGE TITLE
Overview
PAGE SUMMARY
Globally, there are about 37 million people living with HIV/AIDS and 1.2 million died from AIDS-related illnesses in 2014. In the US, over 1.1 million live with HIV/AIDS and 50,000 new cases are reported each year. The HIV therapeutics market was valued at $14.3 billion in 2012 and is expected to reach $16.3 billion by 2019. While highly active anti-retroviral therapy (HAART) is the dominant therapeutic strategy, efficacy would be improved by simultaneous targeting of different stages of the viral life cycle. There are only two FDA-approved therapies that target viral entry, and these molecules are expensive to produce and have limited co-receptor engagement.
Researchers in the Chaiken lab have synthesized multivalent gold nanoparticle conjugates with a peptide triazole entry inhibitor that targets the HIV-1 viral envelope. This conjugate is a potent inhibitor complex that inhibits the HIV-1 pseudovirus at a nM scale in vitro by destabilizing the virus. The peptide triazole inhibitor binds HIV-1 gp120, conformationally trapping the glycoprotein in an inactive state and subsequently blocking host cell CD4 and co-receptor CCR5 and CXCR4 sites. Conjugation of the peptide to gold nanoparticles significantly enhances the therapeutic potency and stability.
APPLICATIONS
TITLE: Applications
HIV-1 entry inhibitor therapy
Irreversibly inactivate HIV-1
Viral lysis of HIV-1 to prevent viral infection in absence of cells
Platform to design nanoparticle-based antiviral agents for HIV-1 derived from macrocyclic peptide triazoles
ADVANTAGES
TITLE:Advantages
Target virus in early stages of disease progression to suppress expansion of HIV-1 in body
Directly inhibit viral replication
High potency and low toxicity in vitro
Complex is readily tracked by microscopy
IP STATUS
Intellectual Property and Development Status
Issued United States Patent 9,114,107
https://patents.google.com/patent/US9114107B2/en
PUBLICATIONS
References
Rashad, A.A. et al. Chemical Optimization of Macrocyclic HIV-1 Inactivators for Improving Potency and Increasing the Structural Diversity at the Triazole Ring. Org. Biomol. Chem., 2017.
http://pubs.rsc.org/en/Content/ArticleLanding/2017/OB/C7OB01448A#!divAbstract
Bastian A.R. et al. Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation. Journal of Biological Chemistry, 2015, 290, p. 529-543.
http://www.jbc.org/content/290/1/529.full?related-urls=yes;290/1/529&290/1/529
Bastian A.R. et al. Cell-free HIV-1 virucidal action by modified peptide triazole inhibitors of Env gp120. ChemMedChem, 2011, 6(8), p. 1335-1318.
http://europepmc.org/articles/PMC3517054
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Contact Information
Tanvi Muni
Licensing Manager
tm3439@drexel.edu