A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.
Nat Commun
; 12(1): 288, 2021 01 12.
Article
in English
| MEDLINE | ID: covidwho-1026824
ABSTRACT
Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Binding
/
Antibodies, Neutralizing
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2021
Document Type:
Article
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