mAbs (Jan 2020)
A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy
- Xiaoniu Miao,
- Yi Luo,
- Xi Huang,
- Suki M. Y. Lee,
- Zhijun Yuan,
- Yongzhou Tang,
- Liandi Chen,
- Chao Wang,
- Fan Wu,
- Yifeng Xu,
- Wenchao Jiang,
- Wei Gao,
- Xuedong Song,
- Yao Yan,
- Tuling Pang,
- Cheng Chen,
- Yuefeng Zou,
- Weihui Fu,
- Liping Wan,
- Javier Gilbert-Jaramillo,
- Michael Knight,
- Tiong Kit Tan,
- Pramila Rijal,
- Alain Townsend,
- Joanne Sun,
- Xiaolin Liu,
- William James,
- Andy Tsun,
- Yingda Xu
Affiliations
- Xiaoniu Miao
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yi Luo
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Xi Huang
- The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
- Suki M. Y. Lee
- New Drug Discovery and Development, Hong Kong Science and Technology Park, China
- Zhijun Yuan
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yongzhou Tang
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Liandi Chen
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Chao Wang
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Fan Wu
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yifeng Xu
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Wenchao Jiang
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Wei Gao
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Xuedong Song
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yao Yan
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Tuling Pang
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Cheng Chen
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yuefeng Zou
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Weihui Fu
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Liping Wan
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Javier Gilbert-Jaramillo
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
- Michael Knight
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
- Tiong Kit Tan
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK
- Pramila Rijal
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK
- Alain Townsend
- Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK
- Joanne Sun
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Xiaolin Liu
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- William James
- Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
- Andy Tsun
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- Yingda Xu
- New Drug Discovery and Development, Biotheus Inc, Zhuhai, China
- DOI
- https://doi.org/10.1080/19420862.2020.1804241
- Journal volume & issue
-
Vol. 12,
no. 1
Abstract
In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.
Keywords
