Potent neutralization of clinical isolates of SARS‑CoV‑2 D614 and G614 variants by a monomeric, sub‑nanomolar affinity nanobody
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2021Metadata
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Valenzuela Nieto, Guillermo
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Potent neutralization of clinical isolates of SARS‑CoV‑2 D614 and G614 variants by a monomeric, sub‑nanomolar affinity nanobody
Author
- Valenzuela Nieto, Guillermo;
- Jara, Ronald;
- Watterson, Daniel;
- Modhiran, Naphak;
- Amarilla, Alberto A.;
- Himelreichs, Johanna;
- Khromykh, Alexander A.;
- Salinas Rebolledo, Constanza;
- Pinto, Teresa;
- Cheuquemilla, Yorka;
- Margolles, Yago;
- López González del Rey, Natalia;
- Miranda Chacón, Zaray;
- Cuevas, Alexei;
- Berking, Anne;
- Deride, Camila;
- González Moraga, Sebastián;
- Mancilla, Héctor;
- Maturana, Daniel;
- Langer, Andreas;
- Toledo, Juan Pablo;
- Müller, Ananda;
- Uberti, Benjamín;
- Krall, Paola;
- Ehrenfeld, Pamela;
- Blesa, Javier;
- Chana Cuevas, Pedro;
- Rehren, Germán;
- Schwefel, David;
- Fernández, Luis Ángel;
- Rojas Fernández, Alejandro;
Abstract
Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to
reduce the burden placed on health systems, the situation remains critical. Effective diagnosis,
treatment, and prophylactic measures are urgently required to meet global demand: recombinant
antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fasttracked
development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the
SARS-CoV-2 Spike protein with potential therapeutic applicability. We present a rapid method for
nanobody isolation that includes an optimized immunization regimen coupled with VHH library E.
coli surface display, which allows single-step selection of Nanobodies using a simple density gradient
centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to
the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor
binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with
IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.
Patrocinador
KOICID
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT 11150532
ID17I10037
3170159
FONIS EU-LAC T010047
PAI-CONICYT 79150075
FONDEQUIO EQM180037
regional Council of the "Los Rios region" FICR16-19
FICR19-20
ISCIII Miguel Servet Program CP19/00200
Graduate fellowship ANID 21161365
ANID 21160481
22170632
University of Costa Rica
Becas Santander Iberoamerica Investigacion 2018/2019
Agencia Espanola de Investigacion AEI/MICIU/FEDER, EU BIO2017-89081-R
CSIC PIE-RDL-COVID-19 (Ministerio de Ciencia e Innovacion from Spain)
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Artículo de publícación WoS Artículo de publicación SCOPUS
Quote Item
Scientific Reports (2021) 11:3318
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