Title: Red Blood Cell-Derived Small Extracellular Vesicles Inhibit Influenza Virus through Surface-Displayed Sialic Acids

Authors: Niangui Cai, Xiaozhen Zhan, Qingyuan Zhang, Haonan Di, Dr. Chen Chen, Dr. Yunyun Hu, Prof. Dr. Xiaomei Yan

Abstract: Disrupting the conserved multivalent binding of hemagglutinin (HA) on influenza A virus (IAV) to sialic acids (SAs) on the host cell membrane offers a robust strategy to block viral attachment and infection, irrespective of antigenic evolution or drug resistance. In this study, we exploit red blood cell-derived small extracellular vesicles (RBC sEVs) as nanodecoys by harnessing their high abundance of surface-displayed SAs to interact with IAV through multivalent HA-SA interactions. This high-avidity binding inhibits viral adhesion to the cell surface, effectively preventing both attachment and infection in a dose-dependent manner. Notably, enzymatic removal of SAs from RBC sEVs significantly diminishes their anti-IAV efficacy. Our findings indicate that RBC sEVs possess intrinsic anti-IAV properties due to their native multivalent SAs and hold considerable promise as antiviral therapeutics.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202413946