Journal
CELL RESEARCH
Volume 31, Issue 1, Pages 25-36Publisher
SPRINGERNATURE
DOI: 10.1038/s41422-020-00444-y
Keywords
-
Categories
Funding
- National Key Research and Development Program [2020YFA0707500, 2018YFA0900801, 2020YFC0848500, 2020YFA0707801]
- National Natural Science Foundation of China (NSFC) [12034006, 82041005, 31900873]
- Beijing Municipal Science and Technology Project [Z201100005420017]
- Major Project of Zhejiang Provincial Science and Technology Department [2020C03123]
- Science and Technology Innovation Action Plan from the Natural Science Foundation of Shanghai [20431900600]
- Ten Thousand Talent Program
- NSFC Innovative Research Group [81921005]
- National Science Fund for Distinguished Young Scholar [81925025]
- NSFC [81621005]
- Innovation Fund for Medical Sciences from the Chinese Academy of Medical Sciences [2019-I2M-5-049]
- Strategic Priority Research Program [XDB29010000]
Ask authors/readers for more resources
This study developed a therapeutic antibody cocktail against SARS-CoV-2 by exploiting antibody cooperativity, consisting of two antibodies that achieved synergistic neutralization through S1 shielding and conformational locking, blocking receptor attachment and viral membrane fusion to combat viral mutation escape. Additionally, a hypothetical third antibody partner was identified for further reinforcement as pan-SARS-CoVs therapeutics.
Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available