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Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease (preprint)
biorxiv; 2021.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2021.01.22.427567
ABSTRACT
Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19). We developed a bispecific, IgG1-like molecule based on two antibodies derived from COVID-19 convalescent donors, C121 and C135. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, completely prevents S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 recognizes a broad panel of RBD variants and neutralizes SARS-CoV-2 and the escape mutants generated by the single monoclonals at sub-nanomolar concentrations. In a novel model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Pneumonia
/
Severe Acute Respiratory Syndrome
/
COVID-19
Language:
English
Year:
2021
Document Type:
Preprint
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