Evidence map›Paper›PMID 32817948›Full record

ArticlebioRxiv : the preprint server for biology2020

Bi-paratopic and multivalent human VH domains neutralize SARS-CoV-2 by targeting distinct epitopes within the ACE2 binding interface of Spike.

Colton J Bracken, Shion A Lim, Paige Solomon, Nicholas J Rettko, Duy P Nguyen, Beth Shoshana Zha, Kaitlin Schaefer, James R Byrnes, Jie Zhou, Irene Lui and 6 more

Abstract 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. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Colton J BrackenDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Shion A LimDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Paige SolomonDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Nicholas J RettkoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Duy P NguyenDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Beth Shoshana ZhaDepartment of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
Kaitlin SchaeferDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
James R ByrnesDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Jie ZhouDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Irene LuiDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Jia LiuDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Katarina PanceDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
QCRG Structural Biology Consortium
Xin X ZhouDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.

Funding

MUTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASEST32HL007185 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle, LAURENCE HUANG · 1985 to 2026
$24.6M
RESEARCH TRAINING IN CHEMISTRY AND CHEMICAL BIOLOGYT32GM064337 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT · 2002 to 2021
$7.8M
Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolutionR35GM122451 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2017 to 2026
$5.3M
Unveiling the Oncogenic Roles of ADAM10/17 by Comprehensively Profiling Proteolytic Activity on a Synthetic Human Protein Peptide Phage LibraryF32CA236151 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZHOU, JIE · 2019 to 2021
$195k
Characterizing and Targeting the Hypoxic T Cell Surfaceome to Promote Immune Function in CancerF32CA239417 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BYRNES, JAMES ROBERT · 2019 to 2021
$191k
NCI NIH HHS F32 CA236151NCI NIH HHS F32 CA239417NHLBI NIH HHS T32 HL007185NIGMS NIH HHS R35 GM122451NIGMS NIH HHS T32 GM064337
6 · The paper itself

Abstract

Neutralizing agents against SARS-CoV-2 are urgently needed for treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domain binders with high affinity toward neutralizing epitopes without the need for high-resolution structural information. We constructed a VH-phage library and targeted a known neutralizing site, the angiotensin-converting enzyme 2 (ACE2) binding interface of the trimeric SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified 85 unique VH binders to two non-overlapping epitopes within the ACE2 binding site on Spike-RBD. This enabled us to systematically link these VH domains into multivalent and bi-paratopic formats. These multivalent and bi-paratopic VH constructs showed a marked increase in affinity to Spike (up to 600-fold) and neutralization potency (up to 1400-fold) on pseudotyped SARS-CoV-2 virus when compared to the standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with half-minimal inhibitory concentration (IC

Identifiers

PMID32817948
PMCPMC7430580

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.