Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants

• DOI: 10.1073/pnas.2201433119
• Publication Date: 2022-04-27T18:23:15Z
• Authors: Jessica Hong; Hyung Joon Kwon; Raul Cachau; Catherine Z. Chen; Kevin John Butay; Zhijian Duan; Dan Li; Hua Ren; Tianyuzhou Liang; Jianghai Zhu; Venkata P. Dandey; Negin P. Martin; Dominic Esposito; Uriel Ortega-Rodr...; Miao Xu; Mario J. Borgnia; Hang Xie; Mitchell Ho
• Keywords: spike protein; Coronavirus

Significance Due to their small size, nanobodies can recognize protein cavities that are not accessible conventional antibodies. In this report, we built dromedary camel ( Camelus dromedarius ) V H phage libraries for the isolation of high-affinity broadly neutralize SARS-CoV-2 variants. Cryo-EM complex structures reveal one nanobody (8A2) binds S1 subunit viral spike protein, and other (7A3) targets a deeply buried region uniquely extends S2 beyond subunit. These protect mice from lethal challenge variants B.1.351 or B.1.617.2, suggesting therapeutic potential these against COVID-19. The could be helpful isolate neutralizing future emerging viruses quickly.