A5029766219- Parasitic Diseases Research and Treatment
- Parasite Biology and Host Interactions
- Trypanosoma species research and implications
- SARS-CoV-2 and COVID-19 Research
- Parasites and Host Interactions
- Research on Leishmaniasis Studies
- Synthesis and Biological Evaluation
- COVID-19 Clinical Research Studies
- Insects and Parasite Interactions
- Helminth infection and control
- Viral gastroenteritis research and epidemiology
- Computational Drug Discovery Methods
- Respiratory viral infections research
- Insect symbiosis and bacterial influences
- SARS-CoV-2 detection and testing
- Long-Term Effects of COVID-19
- Influenza Virus Research Studies
- Animal Virus Infections Studies
- Signaling Pathways in Disease
- Insect and Pesticide Research
- Polymer Nanocomposites and Properties
- Advanced Chemical Sensor Technologies
- Biological Research and Disease Studies
- Additive Manufacturing and 3D Printing Technologies
- Membrane Separation and Gas Transport
Drugs for Neglected Diseases Initiative
2015-2025
Albert Einstein College of Medicine
2020
United States Food and Drug Administration
2020
Johns Hopkins University
2020
Background Human African trypanosomiasis (HAT) is an important public health problem in sub-Saharan Africa, affecting hundreds of thousands individuals. An urgent need exists for the discovery and development new, safe, effective drugs to treat HAT, as existing therapies suffer from poor safety profiles, difficult treatment regimens, limited effectiveness, a high cost goods. We have discovered optimized novel class small-molecule boron-containing compounds, benzoxaboroles, identify SCYX-7158...
Abstract There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally in clinical development. We here report PF-332 exerts equipotent vitro activity four SARS-CoV-2 variants concerns (VoC) it completely arrest replication alpha variant primary human airway epithelial cells grown at air-liquid interface. Treatment Syrian Golden hamsters with (250 mg/kg,...
Since the start of SARS-CoV-2 pandemic, search for antiviral therapies has been at forefront medical research. To date, 3CLpro inhibitor nirmatrelvir (Paxlovid®) shown best results in clinical trials and greatest robustness against variants. A second protease inhibitor, ensitrelvir (Xocova®), developed. Ensitrelvir, currently Phase 3, was approved Japan under emergency regulatory approval procedure November 2022, is available since March 31, 2023. One limitations use monotherapies emergence...
As plans to expand mass drug treatment campaigns fight schistosomiasis form, worries about reliance on praziquantel as the sole available motivate investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of leads.1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration 10 µM. Active identified from this screen advanced adult worm 33.33 µM, followed by hit characterization. Leads with...
ABSTRACT This study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration a murine model Chagas disease. Female Swiss mice infected with Y strain Trypanosoma cruzi were treated orally once per day each metabolite at doses 10 100 mg/kg body weight for period 20 days. Parasitemia monitored throughout, cures detected by parasitological PCR assays. The results compared those achieved benznidazole treatment same doses....
Abstract Porous membranes and dense films were prepared from polysulfone solutions in N ‐methyl‐2‐pyrrolidone (NMP) containing different types amounts of clay. Commercial clays supplied by Southern Clay, either unmodified (Cloisite Na) or organically modified 30B Cloisite 93A), used. The clay behavior the organic solvent was dependent on presence type compatibilizer: Na ions did not swell NMP, whereas those with compatibilizer swelled, though to a degree. Electron microscopy observations...
We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor Trypanosoma cruzi (T. cruzi), causative agent Chagas disease, and results structure–activity investigations leading to potent analogues with low nM IC50s in a T. whole cell vitro assay. Lead compounds suppressed blood parasitemia virtually undetectable levels after once daily oral dosing mouse models infection. Compounds are chemically tractable, allowing rapid optimization target biological activity drug...
Chagas disease, caused by the protozoan pathogen Trypanosoma cruzi, remains a challenging infection due to unavailability of safe and efficacious drugs. Inhibitors trypanosome sterol 14α-demethylase enzyme (CYP51), including azole antifungal drugs, are promising candidates for development as anti-Chagas disease Posaconazole is under clinical investigation although high cost this drug may limit its widespread use. We have previously reported that human protein farnesyltransferase (PFT)...
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in chronic stage disease. We report development two compounds, 6 (S)-7, with PCR-confirmed curative activity a mouse model established T. infection after once daily oral dosing for 20 days at mg/kg 10 (S)-7. Compounds (S)-7 potent vitro activity, are...
A major impediment to eliminate lymphatic filariasis and onchocerciasis is the lack of effective short-course macrofilaricidal drugs or regimens that are proven be safe for both infections. In this study we tested oxfendazole, an anthelmintic shown well tolerated in phase 1 clinical trials. vitro, oxfendazole exhibited modest marginal motility inhibition adult worms Onchocerca gutturosa, pre-adult volvulus lienalis microfilariae. vivo, five days oral treatments provided sterile cure with up...
Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale Necator americanus are limited despite their considerable global health burden. The aim of present study was to test activity an openly available FDA library against laboratory models human intestinal nematode infections. All 1,600 drugs were first screened ceylanicum third-stage larvae (L3). Active compounds scrutinized toxic...
Helminthiases are very prevalent worldwide, yet their treatment and control rely on a handful of drugs. Emodepside, marketed broad-spectrum veterinary anthelminthic with unique mechanism action, undergoing development for onchocerciasis is an interesting anthelmintic drug candidate. We tested the in vitro vivo activity emodepside nematode species that serve as models human soil-transmitted helminth infection well schistosomes. In viability assays were performed over time course 72 hours...
The anti-parasitic benzimidazole flubendazole has been used for many years to treat intestinal infections in humans and animals. Previous genotoxicity studies have shown that the compound is not a bacterial mutagen bone marrow micronucleus test, using formulation limited systemic absorption, was negative. purpose of this study explore its main metabolites vitro test new oral improves absorption an vivo test. isolated were also screened Ames mutagenicity. It found flubendazole, like other...
Filariae are vector-borne nematodes responsible for an enormous burden of disease. Human lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi, and timori, onchocerciasis (caused Onchocerca volvulus) neglected parasitic diseases major public health significance in tropical regions. To date, therapeutic efforts to eliminate human filariasis have been hampered the lack a drug with sufficient macrofilaricidal and/or long-term sterilizing effects that is suitable use mass...
To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence antiviral efficacy.In this work, we present a complete evaluation activity nitazoxanide against SARS-CoV-2.First, confirmed vitro efficacy and tizoxanide (its active metabolite) SARS-CoV-2. Then, demonstrated reconstructed bronchial human airway epithelium model. In SARS-CoV-2 virus challenge...
Background There is an urgent need for improved treatments Chagas disease, a neglected tropical infection caused by the protozoan parasite Trypanosoma cruzi . Benznidazole, first line therapy, has severe limitations such as poor tolerability and variable efficacy in chronic stage of infection. To optimize dosing regimens, better understanding pharmacokinetic/pharmacodynamic (PK/PD) relationship benznidazole crucial. This study aimed to characterize population pharmacokinetic properties mice...
The SARS-CoV-2 pandemic has highlighted the need for broad-spectrum antiviral drugs to respond promptly viral emergence. We conducted a preclinical study of molnupiravir (MOV) against fully characterise its properties and mode action. activity different concentrations MOV was evaluated ex vivo on human airway epithelium (HAE) in hamster model at three escalating doses (150, 300 400 mg/kg/day) according regimens (preventive, pre-emptive curative). assessed loads infectious titres apical pole...