ArticleNature communications2021
A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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.
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.
Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Trial
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- RepurNet: A network medicine framework for systematic drug repurposing and disease vulnerability discovery.iScience · 2026Article
- Pharmacokinetics and safety of nafamostat and its metabolites following single- and multiple-dose oral administration of nafamostat mesylate in healthy male participants.Translational and clinical pharmacology · 2026Article
- LL-37 Inhibits TMPRSS2-Mediated S2' Site Cleavage and SARS-CoV-2 Infection but Not Omicron Variants.Cell proliferation · 2025Article
- ACE-2 blockade and TMPRSS2 inhibition mitigate SARS-CoV-2 severity following cigarette smoke exposure in airway epithelial cellsMolecular therapy. Nucleic acids · 2025Article
- Traditional medicine meets modern science: Halofuginone's role in combating autoimmune diseases.Journal of natural medicines · 2025Review
- Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection.Science advances · 2025Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- Rapid luminescence-based screening method for SARS- CoV-2 inhibitors discovery.SLAS discovery : advancing life sciences R & D · 2025Article
- Impact of Glucose, Inflammation and Phytochemicals onAntioxidants (Basel, Switzerland) · 2025Article
- Selective Control byInternational journal of molecular sciences · 2025Article
- Dissecting the Binding Affinity of Anti-SARS-CoV-2 Compounds to Human Transmembrane Protease, Serine 2: A Computational Study.International journal of molecular sciences · 2025Article
- Anti-inflammatory effects ofFrontiers in pharmacology · 2025Article
- UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting.Neurology international · 2024Article
- NanoLuciferase technology-based detection of TMPRSS2 as attempt to develop anti-coronavirus agents.Biochemistry and biophysics reports · 2024Article
- Sarbecovirus disease susceptibility is conserved across viral and host models.Virus research · 2024Article
- Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.Communications biology · 2024Article
- TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
Corrections and comments
- Update of
Authors and funding
17 authors at 1 institution in 2 countries.
Funding
Abstract
SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.
Indexed as
Identifiers
What OpenQuestion holds
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.