Abstract
According to the World Health Organization, in 2012 there were approximately 35.3 million people living with the Human Immunodeficiency Virus (HIV). HIV has been spreading throughout the world since the late 1970s, and has already claimed the lives of approximately 60 million people. Each year there are 2.3 million people newly infected with the disease and 1.6 million deaths. The current treatment regimen for HIV is a combination therapy called Highly Active Anti-Retroviral Therapy, or HAART. HAART is very expensive and drug resistance can rapidly develop due to a high degree of genetic variability of the HIV virus. To overcome the problems associated with HAART, it is vital that the scientific community works toward developing new HIV inhibitors, and ultimately, a safe and effective a vaccine for this virus. One area of research that shows great promise in the development of potent anti-HIV drugs is the use of polyanionic carbohydrates to inhibit the entry of the HIV virus into host cells. In the current study, sulfated polysaccharides and glycodendrimers were screened for anti-HIV-1 activity via a competitive gp120 binding enzyme-linked immunosorbent assay (ELISA), in hopes of discovering molecules capable of preventing entry of the HIV-1 virion into host cells. The sulfated glycodendrimers and carbohydrates that demonstrated gp120 binding activity in the competitive ELISA were further evaluated by Drs. Celia LaBranche and Norman Chen, both of Duke University, for in vitro live-cell HIV-1 neutralization assays and cellular toxicity profiles, respectively. The molecular characteristics that contribute to effective HIV-1 entry inhibitors were then evaluated. This study has demonstrated the requirement for a minimum of 4% sulfur with 12 sugars on a generation 1 dendrimer core to achieve micromolar inhibition.