January 31, 2000
This presentation reviewed the exciting area of HIV entry and fusion as a target for antiviral drug development. For HIV to establish infection, it must first attach to a host cell and fuse with that cell's outer membrane. Two HIV envelope proteins, gp120 and gp41 -- which mediate binding to cellular receptors and fusion respectively -- facilitate the entry of HIV into the cell. An inhibitor of this process, T20, is already in clinical trials and has shown potent antiretroviral activity even when given to patients who have multiply resistant virus. However, drawbacks to this drug (the first of its class) include the need to administer it intravenously as well as the relatively high doses required for it to achieve inhibition of the binding.
In his presentation, Dr. Kim described how his laboratory has characterized the structure of gp41, especially in the crucial step just before HIV-cellular fusion. Using this information, he and his colleagues have identified a "pocket" on the molecule that would be an ideal target for binding and inhibition of gp41 action. They are currently screening various peptides for their ability to bind to this pocket, which eventually he believes will lead to the discovery of orally bioavailable blockers of HIV entry into cells.