TY - JOUR A1 - Dey, Pradip A1 - Bergmann, Tobias A1 - Cuellar-Camacho, Jose Luis A1 - Ehrmann, Svenja A1 - Chowdhury, Mohammad Suman A1 - Zhang, Minze A1 - Dahmani, Ismail A1 - Haag, Rainer A1 - Azad, Walid T1 - Multivalent flexible nanogels exhibit broad-spectrum antiviral activity by blocking virus entry JF - ACS nano N2 - The entry process of viruses into host cells is complex and involves stable but transient multivalent interactions with different cell surface receptors. The initial contact of several viruses begins with attachment to heparan sulfate (HS) proteoglycans on the cell surface, which results in a cascade of events that end up with virus entry. The development of antiviral agents based on multivalent interactions to shield virus particles and block initial interactions with cellular receptors has attracted attention in antiviral research. Here, we designed nanogels with different degrees of flexibility based on dendritic polyglycerol sulfate to mimic cellular HS. The designed nanogels are nontoxic and broad-spectrum, can multivalently interact with viral glycoproteins, shield virus surfaces, and efficiently block infection. We also visualized virus-nanogel interactions as well as the uptake of nanogels by the cells through clathrin-mediated endocytosis using confocal microscopy. As many human viruses attach to the cells through HS moieties, we introduce our flexible nanogels as robust inhibitors for these viruses. KW - multivalent KW - herpes simplex virus KW - heparan sulfate KW - nanoparticles KW - click chemistry KW - polyglycerol Y1 - 2018 U6 - https://doi.org/10.1021/acsnano.8b01616 SN - 1936-0851 SN - 1936-086X VL - 12 IS - 7 SP - 6429 EP - 6442 PB - American Chemical Society CY - Washington ER -