id author title date pages extension mime words sentences flesch summary cache txt cord-308428-zw26usmh Walter, Justin D. Highly potent bispecific sybodies neutralize SARS-CoV-2 2020-11-10 .txt text/plain 10526 580 54 Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We identified a sybody pair (Sb#15 and Sb#68) that can bind simultaneously to the RBD, and block ACE2 binding, thereby neutralizing pseudotyped and live SARS-CoV-2 viruses. However, binders of the isolated RBD may not effectively engage the aforementioned pre-fusion conformation of the spike protein, which could account for the poor neutralization ability of recently described single-domain antibodies that were raised against the RBD of SARS-CoV-2 spike protein [29] . Since Sb#15 and Sb#68 can bind simultaneously to the RBD and the full-length spike protein, we mixed Sb#15 and Sb#68 together to investigate potential additive or synergistic neutralizing activity of these two independent sybodies. To gain structural insights into how Sb#15 and Sb#68 recognize the RBD, we performed single particle cryo-EM analysis of the spike protein in complex with the sybodies. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 ./cache/cord-308428-zw26usmh.txt ./txt/cord-308428-zw26usmh.txt