Evidence map›Paper›PMID 32587970›Full record

ArticlebioRxiv : the preprint server for biology2020

Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding.

Tyler N Starr, Allison J Greaney, Sarah K Hilton, Katharine H D Crawford, Mary Jane Navarro, John E Bowen, M Alejandra Tortorici, Alexandra C Walls, David Veesler, Jesse D Bloom

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. 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, 181 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Tyler N StarrBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Allison J GreaneyBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Sarah K HiltonBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Katharine H D CrawfordBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Mary Jane NavarroDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
John E BowenDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
M Alejandra TortoriciDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Alexandra C WallsDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
David VeeslerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Jesse D BloomBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
University of Washington · USFred Hutch Cancer Center · USHoward Hughes Medical Institute · US

Funding

Viral Pathogenesis Training ProgramT32AI083203 · NIAID · UNIVERSITY OF WASHINGTON · PI BLOOM, JESSE D, LAGUNOFF, MICHAEL · 2009 to 2023
$2.7M
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteinsR01AI141707 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2018 to 2022
$2.1M
Structural Studies of Coronavirus Fusion ProteinsR01GM120553 · NIGMS · UNIVERSITY OF WASHINGTON · PI VEESLER, DAVID · 2016 to 2020
$1.7M
Complete mapping of the functional and antigenic effects of mutations to Lassa virus glycoproteinF30AI149928 · NIAID · UNIVERSITY OF WASHINGTON · PI CRAWFORD, KATHARINE HOLT DUSENBURY · 2020 to 2021
$91k
NIAID NIH HHS F30 AI149928NIAID NIH HHS HHSN272201700059CNIAID NIH HHS R01 AI141707NIAID NIH HHS T32 AI083203NIGMS NIH HHS R01 GM120553
6 · The paper itself

Abstract

The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor, and is a major determinant of host range and a dominant target of neutralizing antibodies. Here we experimentally measure how all amino-acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD's surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.

Identifiers

PMID32587970
PMCPMC7310626
OpenAlexW3036551549

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.