Synthetic saponins as inhibitors of virus:DC-SIGN interactions

点击翻译按钮获取中文摘要

HIV infections are a significant health issue worldwide. Current antiretroviral therapy is efficient in helping HIV patients to survive, however it remains ineffective in completely removing the virus from the body and can cause undesirable side effects such as residual inflammation. New antiviral strategies against HIV are thus desirable, which is the main focus of this project. Human immunodeficiency virus (HIV) can bind to human dendritic cells through the DC-SIGN receptor, which is specific to certain carbohydrates (i.e., Lewis-X antigens). We propose to chemically prepare natural compounds (i.e., saponins) bearing Lewis-X antigens, which are non-toxic, readily accessible from birch bark residues, and able to self-assemble into micelles. We will evaluate the capacity of these compounds, in both their molecular and supramolecular forms, to bind with the DC-SIGN receptor and to inhibit the DC-SIGN-mediated HIV infection in cellular models. The project will provide new fundamental knowledge on how sugar moieties affect the capacity of saponins to self-assemble and how these synthetic structures could be used to probe and inhibit the interaction of HIV with a human immune receptor of crucial clinical importance. Ultimately, the proposed research project will give access to a new class of agents to help protect against HIV infection.