Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

Lilin Ye; Xiangyu Chen; Ren Li; Zhiwei Pan; Chunfeng Qian; Yang Yang; Renrong You; Jing Zhao; Leiqong Gao; Zhirong Li; Qizhao Huang; Lifan Xu; Jianfang Tang; Qin Tian; Wei Yao; Li Hu; Xiaofeng Yan; Xinyuan Zhou; Pinghuang Liu; Yuzhang Wu; Kai Deng; Zheng Zhang; Yaokai Chen; Zhaohui Qian

The copyright holder for this preprint (which was not peer-reviewed) is . https://doi. org/10.1101 org/10. /2020 Main&text& According! to! World! Health! Organization! (WHO)! newly! updated! situation! report! on! March! 18 th ,! 2020,! the! corona! virus! disease! 2019! (COVID^19)! pandemic! has! confirmed!191,127!cases!and!claimed!7,807!deaths!worldwide 1 .!The!etiological!agent! of!COVID^19!has!been!identified!as!a!novel!coronavirus,!the!severe!acute!respiratory! syndrome!coronavirus!2!(SARS^CoV^2),!belonging!to!Sarbecovirus!subgenus!(genus! Betacoronavirus,! family! Coronaviridae)! and! showing! 79.6%! and! 96.2%! sequence! identity! in! nucleotide! to! SARS^CoV! and! a! bat! coronavirus! (BatCoV! RaTG13),! respectively 2^4 .!Like!SARS^CoV!infection,!a!substantial!fraction!of!COVID^19!patients! exhibits!severe!respiratory!symptoms!and!has!to!be!hospitalized!in!intensive!care!unit! (ICU) 5^8 .! Although! the! mortality! rate! of! COVID^19! is! significantly! lower! than! that! of! SARS^CoV! infection,! SARS^CoV^2! shows! much! higher! human^to^human! transmission!rate,!rapidly!leading!to!a!global!pandemic!declared!by!WHO!on!March! 11 th ,!2020 9 .! ! Currently,!there!are!no!approved!prophylactic!vaccines!or!therapeutic!drugs!that!are! specific! to! COVID^19.! Blocking! monoclonal! antibodies! (mAbs),! due! to! their! extraordinary!antigen!specificity,!are!one!of!the!best!candidates!for!neutralizing!virus! infection 10,!11 .! Therefore,! identifying! and! cloning! blocking! mAbs! that! can! specifically! target! surface! viral! proteins! to! block! the! viral! entry! to! host! cells! is! a! very! attractive! approach!for!preventing!and!treating!COVID^19,!in!particular!when!effective!vaccines! and!therapeutics!are!unavailable!in!the!outbreak!of!the!COVID^19!pandemic.!We!then! sought! to! identify! and! clone! blocking! mAbs! from! the! memory! B! cell! repertoire! of! recently!recovered!COVID^19!patients!to!prevent!the!entry!of!COVID^19!virus!to!the! host!cells.! Similar! to! SARS^CoV,! SARS^CoV^2! also! utilizes! highly! glycosylated! homotrimeric! spike! (S)! protein! for! receptor! binding! and! virus! entry 3,! 12^15 .! The! S! protein! of! SARS^CoV^2! consists! of! two! subunits,! S1! and! S2.! To! engage! host! cell! receptor! All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.