Identification of human single-domain antibodies againstSARS-CoV-2
Yanling Wu,Cheng Li,Shuai Xia,Xiaolong Tian,Yu Kong,Zhi Wang,Chenjian Gu,Rong Zhang,Chao Tu,2 Youhua Xie,1 Zhenlin Yang,3 Lu Lu,1Shibo
Jiang,Tianlei Ying1,4 5 *
SUMMARY
The worldwide spread of COVID-19 highlights the need for an efficient approach torapidly develop therapeutics and prophylactics against SARS-CoV-2. TheSARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1subunit involved in receptor engagement, is a potential therapeutic target. We describethe development of a phage-displayed single-domain antibody library by graftingnaïve complementarity-determining regions (CDRs) into framework regions of ahuman germline immunoglobulin heavy chain variable region (IGHV) allele. Panningthis library against SARS-CoV-2 RBD and S1 subunit identified fully humansingle-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD withsubnanomolar to low nanomolar affinities. Some of these antibodies neutralizeSARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interfaCollectively, this work presents a versatile platform for rapid antibody isolation andidentifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverseimmogneic profile of the spike protein
