ArticleThe Journal of clinical investigation2021
Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Repurposing screens reveal a role for PKCη and NF1 in SARS-CoV-2 infection.PLoS pathogens · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Addressing convergence in the emerging era of structural phylogenetics.Frontiers in molecular biosciences · 2026Article
- An orally available MNature communications · 2025Article
- Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.Science advances · 2024Article
- Anti-SARS-CoV-2 Viral Activity of Sweet Potato Trypsin Inhibitor via Downregulation of TMPRSS2 Activity and ACE2 Expression In Vitro and In Vivo.International journal of molecular sciences · 2024Article
- Exploring the Therapeutic Potential ofMolecules (Basel, Switzerland) · 2024Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening.Analytical chemistry · 2023Article
- BC-11 is a covalent TMPRSS2 fragment inhibitor that impedes SARS-CoV-2 host cell entry.Archiv der Pharmazie · 2023Article
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- Article
- Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2.Microbiology spectrum · 2022Article
- Calpains as mechanistic drivers and therapeutic targets for ocular disease.Trends in molecular medicine · 2022Review
- Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.ACS infectious diseases · 2022Article
- Review
- D3AI-CoV: a deep learning platform for predicting drug targets and for virtual screening against COVID-19.Briefings in bioinformatics · 2022Article
- Article
- A Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19.bioRxiv : the preprint server for biology · 2022Article
- The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS coronavirus 2 (SARS-CoV-2) viral entry and may represent such a target. We hypothesized that drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. We created a structure-based phylogenetic computational tool named 3DPhyloFold to systematically identify structurally similar serine proteases with known therapeutic inhibitors and demonstrated effective inhibition of SARS-CoV-2 infection in vitro and in vivo. Several candidate compounds, avoralstat, PCI-27483, antipain, and soybean trypsin inhibitor, inhibited TMPRSS2 in biochemical and cell infection assays. Avoralstat, a clinically tested kallikrein-related B1 inhibitor, inhibited SARS-CoV-2 entry and replication in human airway epithelial cells. In an in vivo proof of principle, avoralstat significantly reduced lung tissue titers and mitigated weight loss when administered prophylactically to mice susceptible to SARS-CoV-2, indicating its potential to be repositioned for coronavirus disease 2019 (COVID-19) prophylaxis in humans.
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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.