Evidence map›Paper›PMID 40674406›Full record

ArticlePLoS pathogens2025

Membrane-wide screening identifies potential tissue-specific determinants of SARS-CoV-2 tropism.

Ravi K Dinesh, Chengkun Wang, Yuanhao Qu, Arjun Rustagi, Henry Cousins, James Zengel, Xiaotong Wang, Trisha R Barnard, William A Johnson, Guangxue Xu and 13 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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

23 authors.

Ravi K DineshDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Chengkun WangDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Yuanhao QuDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Arjun RustagiDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0002-6921-1012
Henry CousinsDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
James ZengelDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
Xiaotong WangDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Trisha R BarnardDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
William A JohnsonDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Guangxue XuDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Tianyi ZhangDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
Nicholas MagazineDepartment of Pathology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Aimee BeckDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Lucas Miecho HeilbronerDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Grace Peters-SchulzeDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Aaron J WilkDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Mengdi WangDepartment of Electrical and Computer Engineering, Center for Statistics and Machine Learning, Princeton University, Princeton, New Jersey, United States of America.
Weishan HuangDepartment of Pathology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Brooke E HowittDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Jan CaretteMedical Scientist Training Program, Stanford University School of Medicine, Stanford, California, United States of America.
Russ AltmanDepartment of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
Catherine A BlishDivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0001-6946-7627
Le CongDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.ORCID 0000-0003-4725-8714

Funding

Recombineering-based no-cleavage gene-editing toolkit for large-scale genome engineering and functional screeningR01GM141627 · NIGMS · STANFORD UNIVERSITY · PI Le Cong · 2021 to 2026
$3.3M
Towards Robust Multiplex Genome Engineering Beyond CRISPR-Cas9R35HG011316 · NHGRI · STANFORD UNIVERSITY · PI CONG, LE · 2020 to 2025
$2.8M
Computational methods for characterizing sources of variability in drug responseR35GM153195 · NIGMS · STANFORD UNIVERSITY · PI RUSS BIAGIO ALTMAN · 2024 to 2026
$1.0M
Modeling early SARS-CoV-2 pathogenesis in human lung organoids and slice culturesK08AI163369 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUSTAGI, ARJUN · 2022 to 2025
$772k
NHGRI NIH HHS R35 HG011316NIAID NIH HHS K08 AI163369NIGMS NIH HHS R01 GM141627NIGMS NIH HHS R35 GM153195
6 · The paper itself

Abstract

While SARS-CoV-2 primarily infects the respiratory tract, clinical evidence indicates that cells from diverse cell types and organs are also susceptible to infection. Using the CRISPR activation (CRISPRa) approach, we systematically targeted human membrane proteins in cells with and without overexpression of ACE2, thus identifying unrecognized host factors that may facilitate viral entry. Validation experiments with replication-competent SARS-CoV-2 confirmed the role of newly identified host factors, particularly the endo-lysosomal protease legumain (LGMN) and the potassium channel KCNA6, upon exogenous overexpression. In orthogonal experiments, we show that disruption of endogenous LGMN or KCNA6 decreases viral infection and that inhibitors of candidate factors can reduce viral entry. Additionally, using clinical data, we find possible associations between expression of either LGMN or KCNA6 and SARS-CoV-2 infection in human tissues. Our results identify potentially druggable host factors involved in SARS-CoV-2 entry, and demonstrate the utility of focused, membrane-wide CRISPRa screens in uncovering tissue-specific entry factors of emerging pathogens.

Indexed as

COVID-19SARS-CoV-2Viral TropismVirus InternalizationAngiotensin-Converting Enzyme 2Antigens, DifferentiationCRISPR-Cas SystemsHEK293 CellsHumansOrgan SpecificityACE2 protein, humanAngiotensin-Converting Enzyme 2Antigens, Differentiationleu-13 antigen

Identifiers

PMID40674406
PMCPMC12286382

What OpenQuestion holds

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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.