ArticleNature communications2023
Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Nitrile-Based Inhibitors Targeting both SARS-CoV‑2 Main Protease and Human Cathepsin L.ACS medicinal chemistry letters · 2026Article
- Discovery of Highly Selective Noncovalent Macrocyclic Peptide Inhibitors Suppressing Both TMPRSS2 Protease Activity and Viral Receptor Function.Journal of medicinal chemistry · 2026Article
- Development and preclinical evaluation of selective vinyl sulfone-based probes for PET imaging of tumor-associated cathepsins.EJNMMI radiopharmacy and chemistry · 2026Article
- Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human type II transmembrane serine proteases.The Journal of biological chemistry · 2026Article
- 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
- Peptidomimetic α,β-Unsaturated Ethyl Esters Are Irreversible Inactivators of Human Cathepsin L and Are Potent Inhibitors of SARS-CoV-2 in Cellular Models of COVID-19.Journal of medicinal chemistry · 2026Article
- Identification ofRSC medicinal chemistry · 2026Article
- TMPRSS2 is dispensable for lethal SARS-CoV-2 BA.5 infection in humanized hACE2 golden hamsters.European journal of medical research · 2026Article
- Viral mechanisms, tropism, and clinical relevance regarding the ophthalmic manifestations of SARS-CoV-2 infection.International journal of ophthalmology · 2026Review
- Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors.Journal of medicinal chemistry · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases.iScience · 2025Article
- Cholesterol-rich lipid rafts mediate endocytosis as a common pathway for respiratory syncytial virus entry into different host cells.Microbiology spectrum · 2025Article
- The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies.Nature communications · 2025Article
- An orally available MNature communications · 2025Article
- A Dual-Targeting Peptide Inhibitor Simultaneously Blocking Viral Attachment and Membrane Fusion for Broad-Spectrum Inhibition of SARS-CoV-2.International journal of molecular sciences · 2025Article
- Structural basis of TMPRSS11D specificity and autocleavage activation.Nature communications · 2025Article
- The Dynamical Asymmetry in SARS-CoV2 Protease Reveals the Exchange Between Catalytic Activity and Stability in Homodimers.Molecules (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and determine their complex structures with their respective targets. Furthermore, we show that applying inhibitors simultaneously that block both entry pathways has a synergistic antiviral effect. Notably, we devise a bispecific compound, 212-148, exhibiting the dual-inhibition ability of both TMPRSS2 and CTSL/CTSB, and demonstrate antiviral activity against various SARS-CoV-2 variants with different viral entry profiles. Our findings offer an alternative approach for the discovery of SARS-CoV-2 antivirals, as well as application for broad-spectrum treatment of viral pathogenic infections with similar entry pathways.
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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.