A5023291562- Venomous Animal Envenomation and Studies
- Rabies epidemiology and control
- Marine Invertebrate Physiology and Ecology
- Biochemical and Structural Characterization
- Healthcare and Venom Research
- Nicotinic Acetylcholine Receptors Study
- Toxin Mechanisms and Immunotoxins
- SARS-CoV-2 and COVID-19 Research
- Bioactive Natural Diterpenoids Research
- Mosquito-borne diseases and control
- Innovative Microfluidic and Catalytic Techniques Innovation
- Botulinum Toxin and Related Neurological Disorders
- Insect and Pesticide Research
- Entomological Studies and Ecology
- Cancer Treatment and Pharmacology
- vaccines and immunoinformatics approaches
- Doctoral Education Challenges and Solutions
Liverpool School of Tropical Medicine
2020-2025
Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation venom composition dictates different antivenom treatments used parts world, resulting clinical financial snakebite management challenges. Here, we show number repurposed Phase 2-approved small molecules capable broadly...
Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by current antivenoms. Repurposed small molecule drugs that inhibit specific snake venom toxins show considerable promise for tackling this neglected tropical disease. Using human skin cell assays as an initial model snakebite-induced dermonecrosis, we 2,3-dimercapto-1-propanesulfonic acid...
Snakebite envenoming results in ∼100,000 deaths per year, with close to four times as many victims left life-long sequelae. Current antivenom therapies have several limitations including high cost, variable cross-snake species efficacy and a requirement for intravenous administration clinical setting. Next-generation snakebite are being widely investigated the aim improve efficacy, safety. In recent years small molecule drugs shown considerable promise indication, oral bioavailability...
Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often permanent injury via tissue-destructive dermonecrosis at the bite site, which ineffectively treated by current antivenoms. To address this therapeutic gap, we identified etiological toxins in Naja nigricollis responsible for causing local dermonecrosis. While cytotoxic three-finger were primarily cobra cytotoxicity cultured keratinocytes,...
Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause morbidity. Here, we used a pooled whole-genome CRISPR knockout screen define human genes that, when targeted, modify cell responses spitting cobra venoms. A large portion modifying that conferred resistance venom cytotoxicity was found control proteoglycan...
Snakebite claims 138,000 lives a year with an additional 400,000 patients left permanently disabled or disfigured. Morbidity following envenoming includes the development of chronic wounds around bite site. The understanding underlying pathophysiology snakebite has been severely limited by historical reliance on preclinical model that only captures acute local pathology. Through application three medically important snake venoms (Echis ocellatus, Bothrops atrox and Naja nigricollis) to...
Background: Across North America an estimated 3,800 —6,500 snakebite envenomings occur annually, resulting in 7—15 deaths and unknown number of disfigurements disabilities. Most bites are caused by Crotalid rattlesnake species. The variable diversity toxin complexity crotalid venoms presents a considerable challenge to developing broadly effective small molecule therapeutics better treat this region. Methods: We evaluated the ability three molecule, inhibiting, repurposed drugs inhibit venom...
Snakebite envenoming is a neglected tropical disease that causes high mortality and morbidity. The current treatment, intravenous antivenom, comes with numerous disadvantages making new therapeutics important. Optimised small molecules offer the possibility for oral use at onset of envenoming, highly pathogenic, zinc-dependent, snake venom metalloproteinase toxin family represents an attractive target drug discovery. Through systematic chemical modification guided by molecular modelling, we...
Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause variety pathologies in victims, haemotoxic effects are particularly common typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they associated with limited cross-snake species efficacy, as there often extensive toxin variation between...
Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations envenomings vary depending on snake's venom, with paralysis, haemorrhage, necrosis being most common medically relevant effects. To assess efficacy antivenoms against dermonecrosis, preclinical testing approach involves vivo mouse models mimic local tissue effects cytotoxic snakebites humans. However, current...
Abstract Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause variety pathologies in victims, haemotoxic effects are particularly common typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they associated with limited cross-snake species efficacy, as there often extensive toxin...
Abstract Morbidity from snakebite envenoming affects approximately 400,000 people annually. Tissue damage at the bite-site often leaves victims with catastrophic life-long injuries and is largely untreatable by currently available antivenoms. Repurposing small molecule drugs that inhibit specific snake venom toxins offers a potential new treatment strategy for tackling this neglected tropical disease. Using human skin cell assays as an initial model snakebite-induced dermonecrosis, we show...
Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought investigate whether linear epitopes displayed on virus like particles can stimulate an antibody response capable recognising toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding predicted conserved regions group I...
Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and development of deeper understanding how snake venoms exert their toxic effects antivenoms can counter them. However, most our vivo generated knowledge stems from use animal models which do not always accurately reflect pathogenic manifest humans. Moreover, experiments are associated with pain,...
Background: The genus Echis is of high medical importance across Africa. Recently the taxonomy its most medically important species, ocellatus, underwent a revision, resulting in splitting species into E. romani and leading to uncertainty efficacy antivenoms indicated for treatment 'E. ocellatus' envenomings against two redefined species.Methods: We compared vitro murine preclinical venom-neutralising three (EchiTAbG, SAIMR Echiven) raised ocellatus sensu lato venoms investigated...
Abstract Background Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated geographically distinct populations. The puff adder, Bitis arietans , found widely distributed across sub-Saharan Africa into the Arabian Peninsula where it considered a leading cause of ∼310,000 annual snakebites region, its capable causing substantial morbidity mortality. Despite medical importance wide geographic distribution, there little...
Background Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated geographically distinct populations. The puff adder, Bitis arietans , widely distributed across sub-Saharan Africa into the Arabian Peninsula where it considered a leading cause of ~310,000 annual snakebites region, its capable causing substantial morbidity mortality. Despite medical importance wide geographic distribution, there little known about...
Abstract Snakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation venom composition dictates different antivenom treatments used parts world, resulting clinical fiscal snakebite management challenges. Here, we show number repurposed Phase 2-approved small molecules capable...
Abstract Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often permanent injury via tissue-destructive dermonecrosis at the bite site, which ineffectively treated by current antivenoms. To address this therapeutic gap, we identified aetiological toxins responsible for causing local dermonecrosis. While cytotoxic three-finger were primarily cobra cytotoxicity in cultured keratinocytes, their...
Abstract Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations envenomings vary depending on snake’s venom, with paralysis, haemorrhage, necrosis being most common medically relevant effects. To assess efficacy antivenoms against dermonecrosis, preclinical testing approach involves vivo mouse models mimic local tissue effects cytotoxic snakebites humans. However,...
Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought investigate whether linear epitopes displayed on virus like particles can stimulate robust focused antibody response capable recognising toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding predicted conserved regions...