Augusto, Marcelo T.Hollmann, AxelTroise, FulviaVeiga, Ana S.Pessi, AntonelloSantos, Nuno C.2018-06-122018-06-122017Colloids and Surfaces B: Biointerfaces 152 (2017) 311–3160927-7765http://hdl.handle.net/10451/33889© 2017 Elsevier B.VThe HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membraneproximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membraneand this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outsideof the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activityof D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membranebinding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affin-ity of both antibodies towards membranes of different compositions, using surface plasmon resonance. Acorrelation was found between membrane affinity and antiviral activity against HIV-1. We propose thatthe conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at theviral membrane. This way, the antibodies become more available to bind efficiently to the gp41 epitope,blocking viral fusion faster than the unconjugated antibody. These results set up a relevant strategy toimprove the rational design of therapeutic antibodies against HIV.engHIV-1AntibodiesAntiviralSPRMembranejournal article10.1016/j.colsurfb.2017.01.032