Stephen A. Ward
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View article: An accessible 3D HepG2/C3A liver spheroid model supporting the complete intrahepatocytic lifecycle of <i>Plasmodium falciparum</i>
An accessible 3D HepG2/C3A liver spheroid model supporting the complete intrahepatocytic lifecycle of <i>Plasmodium falciparum</i> Open
Current liver-stage Plasmodium falciparum models are complex, expensive and largely inaccessible, hindering research progress. Here, we show that a 3D liver spheroid model grown from immortalized HepG2/C3A cells supports the complete intra…
View article: HIV-1 Amplifies IL-8 Response of Human Stellate Cells to Gram-Positive Microbial Products Via H4K5 Histone Acetylation
HIV-1 Amplifies IL-8 Response of Human Stellate Cells to Gram-Positive Microbial Products Via H4K5 Histone Acetylation Open
Background Patients living with human immunodeficiency virus 1 (PLWH) develop accelerated liver fibrosis, but the exact mechanism remains unknown. Activation of hepatic stellate cells (HSCs)—a cornerstone of fibrosis—is influenced by vario…
View article: An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle of <i>Plasmodium falciparum</i>
An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle of <i>Plasmodium falciparum</i> Open
Current liver-stage Plasmodium falciparum models are complex, expensive, and largely inaccessible, hindering research progress. Here, we show that a 3D liver spheroid model grown from immortalized HepG2/C3A cells supports the complete intr…
View article: P26.05.B DOSE-DEPENDENT DISTRIBUTION OF METHOTREXATE IN THE JUVENILE PIG BRAIN FOLLOWING INTRAVENOUS HIGH-DOSE METHOTREXATE INFUSION
P26.05.B DOSE-DEPENDENT DISTRIBUTION OF METHOTREXATE IN THE JUVENILE PIG BRAIN FOLLOWING INTRAVENOUS HIGH-DOSE METHOTREXATE INFUSION Open
BACKGROUND High-dose methotrexate (HD-MTX) is an essential element in the treatment of numerous cancers, including pediatric acute lymphoblastic leukemia with central nervous system involvement, and malignant brain tumors. However, our und…
View article: Targeting a microbiota <i>Wolbachian</i> aminoacyl-tRNA synthetase to block its pathogenic host
Targeting a microbiota <i>Wolbachian</i> aminoacyl-tRNA synthetase to block its pathogenic host Open
The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or hei…
View article: A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐<i>Wolbachia</i> Candidate Macrofilaricide
A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐<i>Wolbachia</i> Candidate Macrofilaricide Open
AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase…
View article: Combinations of the azaquinazoline anti-Wolbachia agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis
Combinations of the azaquinazoline anti-Wolbachia agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis Open
Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic…
View article: Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in <i>Plasmodium falciparum</i>
Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in <i>Plasmodium falciparum</i> Open
We report the synthesis and biological profiling of photoreactive chemical probes based on an established plasmepsin X inhibitor scaffold. Maintained antimalarial and recombinant enzyme activity support their use in future chemical proteom…
View article: The RNA virome of human and animal parasitic nematodes
The RNA virome of human and animal parasitic nematodes Open
Screening published transcriptomes, we have discovered 75 RNA viruses that infect 27 species of parasitic nematodes, responsible for >1.5 billion infections in people and animals. Our analysis shows extensive diversity and a conserved glob…
View article: Dirofilariasis mouse models for heartworm preclinical research
Dirofilariasis mouse models for heartworm preclinical research Open
Introduction Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug resear…
View article: A dirofilariasis mouse model for heartworm preclinical research
A dirofilariasis mouse model for heartworm preclinical research Open
Use of experimental cats and dogs in veterinary heartworm preclinical drug research is increasing. As a potential alternative primary in vivo heartworm preventative drug screen, we assessed lymphopenic mice with ablation of the interleukin…
View article: Identification of 2-Aryl-Quinolone Inhibitors of Cytochrome <i>bd</i> and Chemical Validation of Combination Strategies for Respiratory Inhibitors against <i>Mycobacterium tuberculosis</i>
Identification of 2-Aryl-Quinolone Inhibitors of Cytochrome <i>bd</i> and Chemical Validation of Combination Strategies for Respiratory Inhibitors against <i>Mycobacterium tuberculosis</i> Open
Mycobacterium tuberculosis cytochrome bd quinol oxidase (cyt bd), the alternative terminal oxidase of the respiratory chain, has been identified as playing a key role during chronic infection and presents a putative target for the developm…
View article: A Quantitative Method for the Study of HIV-1 and<i>Mycobacterium tuberculosis</i>Coinfection
A Quantitative Method for the Study of HIV-1 and<i>Mycobacterium tuberculosis</i>Coinfection Open
Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) syndemic interactions are a major global health concern. Despite the clinical significance of coinfection, our understanding of the cellular pathophysiology and the ther…
View article: Characterization of Lymphocyte Subsets in Lymph Node and Spleen Sections in Fatal Pediatric Malaria
Characterization of Lymphocyte Subsets in Lymph Node and Spleen Sections in Fatal Pediatric Malaria Open
Secondary lymphoid tissues play a major role in the human immune response to P. falciparum infection. Previous studies have shown that acute falciparum malaria is associated with marked perturbations of the cellular immune system character…
View article: Targeting the Ubiquinol-Reduction (Qi) Site of the Mitochondrial Cytochrome bc1 Complex for the Development of Next Generation Quinolone Antimalarials
Targeting the Ubiquinol-Reduction (Qi) Site of the Mitochondrial Cytochrome bc1 Complex for the Development of Next Generation Quinolone Antimalarials Open
Antimalarials targeting the ubiquinol-oxidation (Qo) site of the Plasmodium falciparum bc1 complex, such as atovaquone, have become less effective due to the rapid emergence of resistance linked to point mutations in the Qo site. Recent fi…
View article: <i>Wolbachia</i> depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment
<i>Wolbachia</i> depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment Open
Significance Lymphatic filariasis caused by Wuchereria bancrofti , Brugia malayi , and Brugia timori affects 51 million people, leading to severe physical and mental disabilities. A mutualistic symbiosis between these filarial nematodes an…
View article: Remdesivir–ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2
Remdesivir–ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2 Open
A key element for the prevention and management of coronavirus disease 2019 is the development of effective therapeutics. Drug combination strategies offer several advantages over monotherapies. They have the potential to achieve greater e…
View article: Development of Pyrazolopyrimidine Anti-<i>Wolbachia</i> Agents for the Treatment of Filariasis
Development of Pyrazolopyrimidine Anti-<i>Wolbachia</i> Agents for the Treatment of Filariasis Open
Anti-Wolbachia therapy has been identified as a viable treatment for combating filarial diseases. Phenotypic screening revealed a series of pyrazolopyrimidine hits with potent anti-Wolbachia activity. This paper focuses on the exploration …
View article: Enantioselective Synthesis and Profiling of Potent, Nonlinear Analogues of Antimalarial Tetraoxanes E209 and N205
Enantioselective Synthesis and Profiling of Potent, Nonlinear Analogues of Antimalarial Tetraoxanes E209 and N205 Open
Synthetic endoperoxide antimalarials, such as 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes, are promising successors for current front-line antimalarials, semisynthetic artemisinin derivatives. However, limited solubility of second-generation…
View article: Remdesivir-ivermectin combination displays synergistic interaction with improved<i>in vitro</i>antiviral activity against SARS-CoV-2
Remdesivir-ivermectin combination displays synergistic interaction with improved<i>in vitro</i>antiviral activity against SARS-CoV-2 Open
A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve great…
View article: Therapeutic Potential of Nitazoxanide: An Appropriate Choice for Repurposing versus SARS-CoV-2?
Therapeutic Potential of Nitazoxanide: An Appropriate Choice for Repurposing versus SARS-CoV-2? Open
The rapidly growing COVID-19 pandemic is the most serious global health crisis since the "Spanish flu" of 1918. There is currently no proven effective drug treatment or prophylaxis for this coronavirus infection. While developing safe and …
View article: Recent highlights in antimalarial drug resistance and chemotherapy research
Recent highlights in antimalarial drug resistance and chemotherapy research Open
This review summarizes recent investigations into antimalarial drug resistance and chemotherapy, including reports of some of the many exciting talks and posters on this topic that were presented at the third Molecular Approaches to Malari…
View article: Dose prediction for repurposing nitazoxanide in SARS‐CoV‐2 treatment or chemoprophylaxis
Dose prediction for repurposing nitazoxanide in SARS‐CoV‐2 treatment or chemoprophylaxis Open
Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been declared a global pandemic and urgent treatment and prevention strategies are needed. Nitazoxanide, an anthelmintic drug, has been shown to exhibit in vitro a…
View article: Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis
Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis Open
Background This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictio…
View article: Prioritization of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
Prioritization of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics Open
There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). However, this has not been acc…