The high resolution of the datasets generated to determine the sialic acid–bound HAdV-D26K structure enables visualization of multiple residue conformations with partial occupancy. We demonstrate that removal of cell surface sialic acid inhibits HAdV-D26 infection, and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid. Here, we establish sialic acid as a primary entry receptor used by HAdV-D26. We recently demonstrated that HAdV-D26 does not use CD46 or Desmoglein-2 as entry receptors, while the putative interaction with coxsackie and adenovirus receptor is low affinity and unlikely to represent the primary cell receptor. HAdV-D26–derived vaccines are under investigation as protective platforms against HIV, Zika, and respiratory syncytial virus infections and are in phase 3 clinical trials for Ebola. Species D adenovirus type 26 (HAdV-D26) is both a cause of EKC and other diseases and a promising vaccine vector. As non-enveloped, double-stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. ![]() ![]() They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. Adenoviruses are clinically important agents.
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