Evidence map›Paper›PMID 33154108›Full record

ArticleScience (New York, N.Y.)2020

Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2.

Yufei Xiang, Sham Nambulli, Zhengyun Xiao, Heng Liu, Zhe Sang, W Paul Duprex, Dina Schneidman-Duhovny, Cheng Zhang, Yi Shi

Open access · hybridAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 1 pooled it
38.4field-weighted citation impact, top 1% of its field
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

243 citing papers in PubMed, 1 synthesis or guideline pooled it, 441 citations in OpenAlex.

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183 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Yufei XiangDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0002-6732-5649
Sham Nambulli *Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0002-9781-9703
Zhengyun Xiao *Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0003-2672-1597
Heng Liu *Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0003-2654-4287
Zhe SangDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0002-1516-2796
W Paul DuprexCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.ORCID https://orcid.org/0000-0003-1716-6376
Dina Schneidman-DuhovnySchool of Computer Science and Engineering, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel. dina.schneidman@mail.huji.ac.il chengzh@pitt.edu yi.shi@pitt.edu.ORCID https://orcid.org/0000-0003-0480-0438
Cheng ZhangDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. dina.schneidman@mail.huji.ac.il chengzh@pitt.edu yi.shi@pitt.edu.ORCID https://orcid.org/0000-0001-9042-4007
Yi ShiDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA. dina.schneidman@mail.huji.ac.il chengzh@pitt.edu yi.shi@pitt.edu.ORCID https://orcid.org/0000-0002-2761-8324
University of Pittsburgh · USHebrew University of Jerusalem · IL

Funding

Practices CoreUC7AI180311 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI William Paul Duprex · 2023 to 2026
$13.2M
Structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) in inflammationR35GM128641 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHENG ZHANG · 2018 to 2026
$3.5M
Development of multivalent, ultrapotent nanobody cocktails for SARS-CoV-2 neutralizationR01AI163011 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI William Paul Duprex, Yi Shi · 2022 to 2026
$3.1M
Mapping the Dynamic Interactome of Ig-fold Membrane Proteins Using Nanobody-Based ToolsR35GM137905 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yi Shi · 2020 to 2026
$2.8M
NIAID NIH HHS R01 AI163011NIAID NIH HHS UC7 AI180311NIGMS NIH HHS R35 GM128641NIGMS NIH HHS R35 GM137905
6 · The paper itself

Abstract

Cost-effective, efficacious therapeutics are urgently needed to combat the COVID-19 pandemic. In this study, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD). We discovered Nbs with picomolar to femtomolar affinities that inhibit viral infection at concentrations below the nanograms-per-milliliter level, and we determined a structure of one of the most potent Nbs in complex with the RBD. Structural proteomics and integrative modeling revealed multiple distinct and nonoverlapping epitopes and indicated an array of potential neutralization mechanisms. We bioengineered multivalent Nb constructs that achieved ultrahigh neutralization potency (half-maximal inhibitory concentration as low as 0.058 ng/ml) and may prevent mutational escape. These thermostable Nbs can be rapidly produced in bulk from microbes and resist lyophilization and aerosolization.

Indexed as

Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralAntibody AffinityCamelids, New WorldCOVID-19Escherichia coliHumansNeutralization TestsProtein BindingProtein DomainsReceptors, VirusRecombinant ProteinsSARS-CoV-2Single-Domain AntibodiesAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralReceptors, VirusRecombinant ProteinsSingle-Domain Antibodies

Identifiers

PMID33154108
PMCPMC7857400
OpenAlexW3095441755

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.