Evidence map›Paper›PMID 32817938›Full record

ArticlebioRxiv : the preprint server for biology2020

An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation.

Michael Schoof, Bryan Faust, Reuben A Saunders, Smriti Sangwan, Veronica Rezelj, Nick Hoppe, Morgane Boone, Christian B Billesbølle, Cristina Puchades, Caleigh M Azumaya and 47 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

57 authors at 7 institutions in 2 countries.

Michael SchoofHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Bryan FaustHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Reuben A SaundersHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Smriti SangwanHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Veronica RezeljViral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724, Paris, Cedex 15, France.
Nick HoppeDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Morgane BooneHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Christian B BillesbølleDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Cristina PuchadesQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Caleigh M AzumayaQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Huong T KratochvilQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Marcell ZimanyiHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Ishan DeshpandeDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Jiahao LiangDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Sasha DickinsonQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Henry C NguyenQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Cynthia M ChioQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Gregory E MerzQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Michael C ThompsonQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Devan DiwanjiQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Kaitlin SchaeferQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Aditya A AnandHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Niv DobzinskiHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Beth Shoshana ZhaDepartment of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
Camille R SimoneauQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Kristoffer LeonQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Kris M WhiteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Un Seng ChioQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Meghna GuptaQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Mingliang JinQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Fei LiQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Yanxin LiuQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Kaihua ZhangQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
David BulkleyQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Ming SunQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Amber M SmithQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Alexandrea N RizoQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Frank MossQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Axel F BrilotQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Sergei PourmalQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Raphael TrenkerQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Thomas PospiechQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Sayan GuptaMolecular Biophysics and Integrated Bioimaging and the Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Benjamin Barsi-RhyneDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Vladislav BelyyHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Andrew W Barile-HillCytiva Life Sciences, Marlborough, MA, USA.
Silke NockHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Yuwei LiuHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Nevan J KroganQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Corie Y RalstonMolecular Biophysics and Integrated Bioimaging and the Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Danielle L SwaneyQuantitative Biosciences Institute (QBI) Coronavirus Research Group Structural Biology Consortium, University of California, San Francisco, CA, USA.
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Melanie OttQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
Marco VignuzziViral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724, Paris, Cedex 15, France.
QCRG Structural Biology Consortium
Peter WalterHoward Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA.
Aashish ManglikDepartment of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, CA, USA.
Quantitative BioSciences · USHoward Hughes Medical Institute · USUniversity of California, San Francisco · USGladstone Institutes · USCentre National de la Recherche Scientifique · FRIcahn School of Medicine at Mount Sinai · USLawrence Berkeley National Laboratory · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Technology Development Project - Increasing the complexity of ex vivo human airway models for studying immune response to viral infectionU19AI142733 · NIAID · JACKSON LABORATORY · PI Adolfo Garcia-Sastre, Anna Karolina Palucka · 2019 to 2026
$23.1M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Development of high-dose time-resolved x-ray footprinting technologies to enable the next level of structural analysis for challenging biological problemsR01GM126218 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI RALSTON, CORIE Y · 2018 to 2025
$3.4M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Molecular Mechanisms of Iron HomeostasisDP5OD023048 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MANGLIK, AASHISH · 2016 to 2020
$2.0M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
A structural and biophysical study of the matrix proteins in influenza A/B viruses: Mechanisms of proton conduction and roles of protein-protein interactionsF32GM125217 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRATOCHVIL, HUONG TRAN · 2017 to 2019
$177k
Understanding the Role of RNA Surveillance Mechanisms in Neuropathogenesis during Zika Virus InfectionF31NS113432 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEON, KRISTOFFER E · 2019 to 2020
$69k
NIAID NIH HHS HHSN272201400008CNIAID NIH HHS U19 AI142733NIGMS NIH HHS F32 GM125217NIGMS NIH HHS R01 GM126218NIGMS NIH HHS T32 GM007618NIGMS NIH HHS T32 GM008284NIH HHS DP5 OD023048NIH HHS S10 OD020054NIH HHS S10 OD021741NINDS NIH HHS F31 NS113432
6 · The paper itself

Abstract

Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century.

Identifiers

PMID32817938
PMCPMC7430568
OpenAlexW3048783206

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.