Identification of nurse shark VNAR single‐domain antibodies targeting the spike S2 subunit of SARS‐CoV‐2

• DOI: 10.1096/fj.202202099rr
• Publication Date: 2023-05-16T15:29:56Z
• Authors: Jesse Buffington; Zhijian Duan; Hyung Joon Kwon; Jessica Hong; Dan Li; Mingqian Feng; Hang Xie; Mitchell Ho
• Keywords: Panning (audio); spike protein; Coronavirus

Abstract SARS‐CoV‐2 is the etiological agent of COVID‐19 pandemic. Antibody‐based therapeutics targeting spike protein, specifically S1 subunit or receptor binding domain (RBD) SARS‐CoV‐2, have gained attention due to their clinical efficacy in treating patients diagnosed with COVID‐19. An alternative conventional antibody use shark new antigen variable (V NAR ) antibodies. V s are small (<15 kDa) and can reach deep into pockets grooves target antigen. Here, we isolated 53 that bind S2 by phage panning from a naïve nurse display library constructed our laboratory. Among those binders, S2A9 showed best neutralization activity against original pseudotyped virus. Several including S2A9, cross‐reactivity subunits other β coronaviruses. Furthermore, all variants concern (VOCs) alpha omicron (including BA1, BA2, BA4, BA5) both pseudovirus live virus assays. Our findings suggest could be promising lead molecule for development broadly neutralizing antibodies emerging variants. The offers novel platform used rapidly isolate single‐domain viral pathogens.