ArticleAntimicrobial agents and chemotherapy2007
A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 185 citations in OpenAlex.
- Article
- Cruzain Inhibitors for Chagas Disease: Anticorrelated Optimisation Landscapes and the Multiparametric Path to Clinical Candidates.Chemical biology & drug design · 2026Review
- Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease.Memorias do Instituto Oswaldo Cruz · 2025Article
- Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Screening the Pathogen Box to Discover and Characterize New Cruzain andPathogens (Basel, Switzerland) · 2023Article
- Covalent Warheads Targeting Cysteine Residue: The Promising Approach in Drug Development.Molecules (Basel, Switzerland) · 2022Review
- Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications.Brain pathology (Zurich, Switzerland) · 2022Review
- De Novo Design of Cathepsin B1 Inhibitors as Potential Anti-Schistosomal Agents Using Computational Studies.Advances and applications in bioinformatics and chemistry : AABC · 2022Article
- Self-Masked Aldehyde Inhibitors of Human Cathepsin L Are Potent Anti-CoV-2 Agents.Frontiers in chemistry · 2022Article
- In vitro Leishmanicidal and Trypanosomicidal Properties of Imidazole-Containing Azine and Benzoazine Derivatives.ChemMedChem · 2021Article
- Host-parasite dynamics in Chagas disease from systemic to hyper-local scales.Parasite immunology · 2021Review
- Repurposing Carvedilol as a Novel Inhibitor of theFrontiers in cellular and infection microbiology · 2021Article
- Review on Experimental Treatment Strategies AgainstJournal of experimental pharmacology · 2021Review
- An Overview on the Therapeutics of Neglected Infectious Diseases-Leishmaniasis and Chagas Diseases.Frontiers in chemistry · 2021Review
- Drug Repurposing Approaches to Combating Viral Infections.Journal of clinical medicine · 2020Review
- A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells.bioRxiv : the preprint server for biology · 2020Article
- Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients.Pharmacology & therapeutics · 2020Review
- Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity.Journal of medicinal chemistry · 2020Article
- Discovery and characterization of trypanocidal cysteine protease inhibitors from the 'malaria box'.European journal of medicinal chemistry · 2019Article
- Catalytic Mechanism of Cruzain from Trypanosoma cruzi As Determined from Solvent Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.Biochemistry · 2018Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chagas' disease, caused by the parasite Trypanosoma cruzi, remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of T. cruzi. The inhibitor N-methyl-Pip-F-homoF-vinyl sulfonyl phenyl (N-methyl-Pip-F-hF-VS phi) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1(-/-)) and normal mice infected with T. cruzi. Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1(-/-) mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide N-methyl-Pip-F-hF-VS phi rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1(-/-) mice had increased survival, negative PCR, and normal tissues by histopathological examination.
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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.