Evidence map›Paper›PMID 41982337›Full record

ArticlebioRxiv : the preprint server for biology2025

A SARS-CoV-2 entry inhibitor trimerizes to lock the spike protein in a closed conformation.

Huihui Mou, Bo Gao, Gang Ye, Lizhou Zhang, Divyasha Saxena, Fan Bu, Jyoti Vishwakarma, Shuo Zhou, Claudia Ruiz Bayona, Li Lin and 21 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Target discovery and drug design in the era of artificial intelligence.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors.

Huihui MouDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Bo GaoDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Gang YeDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
Lizhou ZhangDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-2637-9712
Divyasha SaxenaDepartment of Microbiology and Immunology, Center for Predictive Medicine, University of Louisville, Louisville, KY, USA.
Fan BuDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
Jyoti VishwakarmaDepartment of Biochemistry and Structural Biology, University of Texas San Antonio, San Antonio, TX, USA.
Shuo ZhouDepartment of Biochemistry and Structural Biology, University of Texas San Antonio, San Antonio, TX, USA.
Claudia Ruiz BayonaDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Li LinDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Yulia GetmanenkoDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Janarjan BhandariThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Charles C BaileyThe Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gogce C CrynenBioinformatics and Statistics Core Facility, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Claire E KitzmillerDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Hao LiDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Yuka OtsukaDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Chao WangDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Lalit BatraDepartment of Microbiology and Immunology, Center for Predictive Medicine, University of Louisville, Louisville, KY, USA.
Stuart WestonCenter for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Matthew B FriemanCenter for Pathogen Research, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
David K MeyerholzDepartment of Pathology, University of Iowa, Iowa City, IA, USA.
Louis ScampaviaDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Timothy P SpicerDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Reuben S HarrisDepartment of Biochemistry and Structural Biology, University of Texas San Antonio, San Antonio, TX, USA.ORCID 0000-0002-9034-9112
Michael D CameronDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Thomas D BannisterDepartment of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA.
Jian ZhengDepartment of Microbiology and Immunology, Center for Predictive Medicine, University of Louisville, Louisville, KY, USA.
Michael FarzanDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Fang LiDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
Hyeryun ChoeDivision of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.

Funding

Targeting druggable coronavirus proteinsU19AI171443 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI SUMIT K CHANDA, Arnab Kumar Chatterjee · 2022 to 2026
$101.4M
Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Reuben S Harris, Fang Li · 2022 to 2026
$100.9M
NIAID NIH HHS U19 AI171443NIAID NIH HHS U19 AI171954
6 · The paper itself

Abstract

The SARS-CoV-2 spike protein binds its receptor ACE2 to initiate target-cell infection. To engage ACE2, at least one of the three receptor-binding domains (RBDs) of the spike must adopt the up orientation. Here we describe S22, a potent, bioavailable, and non-toxic inhibitor of BA.2 and all subsequent Omicron variants. Cryo-EM analyses showed that S22 assembled as a trimer in a previously uncharacterized pocket of the spike apex, stabilizing all three RBDs in the down orientation, thereby preventing ACE2 association. Binding studies, especially those using mixed S22-sensitive and -resistant spikes, imply a cooperative assembly of three S22 molecules with three RBDs, resulting in an unusually slow S22 off-rate. Consistent with its slow dissociation and favorable pharmacokinetics, S22 suppressed viral replication 100-fold in the lungs of XBB.1.5-infected mice. Thus, S22 potently inhibits Omicron entry through a distinct mechanism whereby a small compound assembles cooperatively as a trimer to stabilize spike in an inactive conformation.

Identifiers

PMID41982337
PMCPMC13073230

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.