Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 1 of 1
Full-Text Articles in Medical Molecular Biology
Complex Interplay Of Kinetic Factors Governs The Synergistic Properties Of Hiv-1 Entry Inhibitors., Koree W. Ahn, Michael J. Root
Complex Interplay Of Kinetic Factors Governs The Synergistic Properties Of Hiv-1 Entry Inhibitors., Koree W. Ahn, Michael J. Root
Department of Biochemistry and Molecular Biology Faculty Papers
The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by …