ArticleMolecular pharmacology2010
A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 121 citations in OpenAlex.
- Cathepsin L and transmembrane serine protease 11E mediate trypsin-independent entry of porcine deltacoronavirus into Huh7 cells.Journal of virology · 2025Article
- Advancements in the development of antivirals against SARS-Coronavirus.Frontiers in cellular and infection microbiology · 2025Review
- Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors.Journal of medicinal chemistry · 2024Article
- Host serine protease ACOT2 assists DENV proliferation by hydrolyzing viral polyproteins.mSystems · 2024Article
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- Identification of Z-Tyr-Ala-CHNMicroorganisms · 2023Article
- COVID-19 signalome: Potential therapeutic interventions.Cellular signalling · 2023Review
- An insight into SARS-CoV-2 structure, pathogenesis, target hunting for drug development and vaccine initiatives.RSC medicinal chemistry · 2022Review
- Andrographolide induces anti-SARS-CoV-2 response through host-directed mechanism: anFuture virology · 2022Article
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L.Journal of medicinal chemistry · 2022Article
- Structural biology of SARS-CoV-2: open the door for novel therapies.Signal transduction and targeted therapy · 2022Review
- COVID-19: A review of newly formed viral clades, pathophysiology, therapeutic strategies and current vaccination tasks.International journal of biological macromolecules · 2021Review
- Potential therapeutic approaches for the early entry of SARS-CoV-2 by interrupting the interaction between the spike protein on SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2).Biochemical pharmacology · 2021Review
- Targeting the viral-entry facilitators of SARS-CoV-2 as a therapeutic strategy in COVID-19.Journal of medical virology · 2021Review
- Phyto-pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID-19, based on its promising immunomodulatory, anti-coagulant and anti-viral property.Phytotherapy research : PTR · 2021Review
- Severe acute respiratory syndrome-coronavirus-2: Current advances in therapeutic targets and drug development.Reviews in medical virology · 2021Review
- Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development.Signal transduction and targeted therapy · 2021Article
- The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2.European journal of medicinal chemistry · 2021Review
20 more citing papers are in PubMed but not listed here.
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11 authors at 1 institution in 1 country.
Funding
Abstract
A tetrahydroquinoline oxocarbazate (PubChem CID 23631927) was tested as an inhibitor of human cathepsin L (EC 3.4.22.15) and as an entry blocker of severe acute respiratory syndrome (SARS) coronavirus and Ebola pseudotype virus. In the cathepsin L inhibition assay, the oxocarbazate caused a time-dependent 17-fold drop in IC(50) from 6.9 nM (no preincubation) to 0.4 nM (4-h preincubation). Slowly reversible inhibition was demonstrated in a dilution assay. A transient kinetic analysis using a single-step competitive inhibition model provided rate constants of k(on) = 153,000 M(-1)s(-1) and k(off) = 4.40 x 10(-5) s(-1) (K(i) = 0.29 nM). The compound also displayed cathepsin L/B selectivity of >700-fold and was nontoxic to human aortic endothelial cells at 100 muM. The oxocarbazate and a related thiocarbazate (PubChem CID 16725315) were tested in a SARS coronavirus (CoV) and Ebola virus-pseudotype infection assay with the oxocarbazate but not the thiocarbazate, demonstrating activity in blocking both SARS-CoV (IC(50) = 273 +/- 49 nM) and Ebola virus (IC(50) = 193 +/- 39 nM) entry into human embryonic kidney 293T cells. To trace the intracellular action of the inhibitors with intracellular cathepsin L, the activity-based probe biotin-Lys-C5 alkyl linker-Tyr-Leu-epoxide (DCG-04) was used to label the active site of cysteine proteases in 293T lysates. The reduction in active cathepsin L in inhibitor-treated cells correlated well with the observed potency of inhibitors observed in the virus pseudotype infection assay. Overall, the oxocarbazate CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells.
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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.