ArticleNature chemical biology2022
Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 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
129 citing papers in PubMed, 201 citations in OpenAlex.
- Intranasal drop of multiplex RNA therapy for SARS-CoV-2 infections: baicalein-enhanced FEN1 nuclease cleaving as a virus buster.Emerging microbes & infections · 2026Article
- Article
- Discovery of Highly Selective Noncovalent Macrocyclic Peptide Inhibitors Suppressing Both TMPRSS2 Protease Activity and Viral Receptor Function.Journal of medicinal chemistry · 2026Article
- Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches.Molecules (Basel, Switzerland) · 2026Review
- Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human type II transmembrane serine proteases.The Journal of biological chemistry · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Human angiotensin‑converting enzyme 2‑specific benzothiazole-based allosteric inhibitor against pan‑sarbecoviruses.Nature communications · 2026Article
- TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.EMBO reports · 2026Article
- Pilot survey among patients taking bromhexine prophylactically against influenza.Journal of family medicine and primary care · 2026Article
- Epithelial TMPRSS2 impairs glucose homeostasis in obese mice by regulating ghrelin-GLP-1 receptor signaling pathway.JCI insight · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- 3-Amidinophenylalanine-Derived Inhibitors' Antiviral Effect Against H1N1 Influenza A Virus.Antibiotics (Basel, Switzerland) · 2026Article
- A novel fusion protein of COVID-19 virus enhancing protection of Syrian hamsters infected with SARS-CoV-2.Acta pharmaceutica Sinica. B · 2026Article
- SARS-CoV-2-host and interactions: the dual roles of E3 ubiquitin ligases and ubiquitin-like modification mechanisms in viral infection.Frontiers in immunology · 2026Review
- Differential Evolution for Docking Simulations.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Serine protease-driven entry and S2 ' cleavage flexibility of feline coronavirus during feline enterocyte infections.PLoS pathogens · 2026Article
- Searching for Novel Antiviral Agents as COVID19 Treatments: Guanidino Diaryl Thioureas.ChemMedChem · 2026Article
- Efficient production of fully active, SARS-CoV-2-priming, wildtype TMPRSS2 ectodomain via co-expression of HAI-2 allows for both auto- and cross-activation mechanisms.The Biochemical journal · 2025Article
- LL-37 Inhibits TMPRSS2-Mediated S2' Site Cleavage and SARS-CoV-2 Infection but Not Omicron Variants.Cell proliferation · 2025Article
- In Silico Analysis of CMolecules (Basel, Switzerland) · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Transmembrane protease, serine 2 (TMPRSS2) has been identified as key host cell factor for viral entry and pathogenesis of SARS-CoV-2. Specifically, TMPRSS2 proteolytically processes the SARS-CoV-2 Spike (S) protein, enabling virus-host membrane fusion and infection of the airways. We present here a recombinant production strategy for enzymatically active TMPRSS2 and characterization of its matured proteolytic activity, as well as its 1.95 Å X-ray cocrystal structure with the synthetic protease inhibitor nafamostat. Our study provides a structural basis for the potent but nonspecific inhibition by nafamostat and identifies distinguishing features of the TMPRSS2 substrate binding pocket that explain specificity. TMPRSS2 cleaved SARS-CoV-2 S protein at multiple sites, including the canonical S1/S2 cleavage site. We ranked the potency of clinical protease inhibitors with half-maximal inhibitory concentrations ranging from 1.4 nM to 120 µM and determined inhibitor mechanisms of action, providing the groundwork for drug development efforts to selectively inhibit TMPRSS2.
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.