ArticleThe Journal of clinical investigation2026
Targeting the host factor HGS-viral membrane protein interaction in coronavirus infection.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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Who cites it
7 citing papers in PubMed.
- Thrombospondin-1 as a Mechanosensitive Matrix Protein Driving Fibroblast Senescence: A Novel Pathogenic Target for Pelvic Organ Prolapse.International urogynecology journal · 2026Article
- TRIM65 accelerates VSMC-derived foam cell formation and arteriosclerosis progression by inhibiting mitophagy.Molecular and cellular biochemistry · 2026Article
- Piezo1-A Key Pathogenic Factor in Breast Implant-Associated Capsular Contracture.Aesthetic plastic surgery · 2026Article
- Tirzepatide mitigates atherosclerosis progression and modulates oxLDL-mediated proatherogenic effects in macrophages: evidence for M1/M2 homeostasis restoration.Archives of pharmacal research · 2026Article
- How the host becomes the target: exploiting an intracellular transport pathway to treat coronaviruses.The Journal of clinical investigation · 2026Article
- Integrative bioinformatics-machine learning-experimental validation identifies shared immunomodulatory targets in psoriasis and psoriatic arthritis and deciphers allicin's therapeutic mechanism.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Genetic Evidence Linking Lactylation-Related Gene Expression To Dementia Risk.Neuromolecular medicine · 2025Article
Corrections and comments
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Authors and funding
28 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While current antivirals primarily target viral proteins, host-directed strategies remain underexplored. Here, we performed a genome-wide CRISPR inhibition (CRISPRi) screening to identify the host protein, hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), facilitating the pan-coronavirus infection both in vitro and in vivo. Mechanistically, HGS interacts with the viral membrane (M) protein, facilitating its trafficking to the ER-Golgi intermediate compartment for virion assembly. Conversely, HGS deficiency caused M retention in the ER, blocking assembly. Leveraging this interaction, we designed M-derived peptides and screened over 5,000 FDA-approved or commonly used drugs, identifying riboflavin tetrabutyrate (RTB). Both the peptides and RTB bind HGS and disrupt its interaction with the M protein, leading to M retention in the ER and subsequent blockade of virion assembly. These agents demonstrated broad anti-pan-coronavirus activity in vitro and in vivo. Collectively, our findings establish HGS as a druggable host target and identify RTB as a promising broad-spectrum antiviral candidate.
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Registered trials
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.