Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2.
Sci Rep
; 10(1): 17806, 2020 10 20.
Article
in English
| MEDLINE | ID: covidwho-882927
ABSTRACT
SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Single-Domain Antibodies
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
Type of study:
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Sci Rep
Year:
2020
Document Type:
Article
Affiliation country:
S41598-020-74761-y
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