Anthelmintic discovery and development in the animal health industry

Woods, Debra J.; Lauret, Christelle; Geary, Timothy G.

doi:10.1517/17460441.2.s1.s25

Cited by 36 publications

(19 citation statements)

References 31 publications

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“…Current programs of anthelmintic drug discovery, especially those that operate in industrial settings, focus primarily on the discovery of new drugs for veterinary indications: mainly gastrointestinal nematodes of livestock and companion animals, and canine heartworm (Woods et al., 2007, Woods et al., 2011, Woods and Knauer, 2010, Geary et al., 2015). Furthermore, it is worthy of note that many of the anthelmintics used in human medicine were originally developed for the veterinary sector (Geary et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in ion channel genes of Dirofilaria immitis : Relevant knowledge for future anthelmintic drug design

Mani

Bourguinat

Keller

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML) class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D. immitis and thus there is an urgent need to find new anthelmintics that could prevent and/or control the disease. Targeting ion channels of D. immitis for drug design has obvious advantages. These channels, present in the nematode nervous system, control movement, feeding, mating and respond to environmental cues which are necessary for survival of the parasite. Any new drug that targets these ion channels is likely to have a motility phenotype and should act to clear the worms from the host. Many of the successful anthelmintics in the past have targeted these ion channels and receptors. Knowledge about genetic variability of the ion channel and receptor genes should be useful information for drug design as receptor polymorphism may affect responses to a drug. Such information may also be useful for anticipation of possible resistance development. A total of 224 ion channel genes/subunits have been identified in the genome of D. immitis. Whole genome sequencing data of parasites from eight different geographical locations, four from ML-susceptible populations and the other four from ML-loss of efficacy (LOE) populations, were used for polymorphism analysis. We identified 1762 single nucleotide polymorphic (SNP) sites (1508 intronic and 126 exonic) in these 224 ion channel genes/subunits with an overall polymorphic rate of 0.18%. Of the SNPs found in the exon regions, 129 of them caused a non-synonymous type of polymorphism. Fourteen of the exonic SNPs caused a change in predicted secondary structure. A few of the SNPs identified may have an effect on gene expression, function of the protein and resistance selection processes.

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Section: Introductionmentioning

confidence: 99%

Polymorphism in ion channel genes of Dirofilaria immitis : Relevant knowledge for future anthelmintic drug design

Mani

Bourguinat

Keller

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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“…Because so few effective antifilarial drugs exist, the same drugs have been commonly used to treat both human and animal helminth diseases for more than three decades. 2 Consequently, drug resistance has emerged clinically around the world, underscoring the clear need to identify antiparasite agents with new, alternative modes of action. 3 …”

mentioning

confidence: 99%

New WS9326A Congeners from Streptomyces sp. 9078 Inhibiting Brugia malayi Asparaginyl-tRNA Synthetase

Vodanovic-Jankovic

Kron

et al. 2012

Org. Lett.

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Lymphatic filariasis is caused by the Brugia malayi parasite. Three new congeners of the depsipeptide WS9326A (1), WS9326C (2), WS9326D (3) and WS9326E (4), were isolated from Streptomyces sp. 9078 by using a B. malayi asparaginyl-tRNA synthetase (BmAsnRS) inhibition assay. WS9326D specifically inhibits the BmAsnRS, kills the adult B. malayi parasite, and does not exhibit significant general cytotoxicity to human hepatic cells, representing a new lead scaffold for antifilarial drug discovery.

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“…Empirical research continues to be the foundation of the discovery of anthelmintic agents (Woods et al 2007;Woods and Knauer, 2010;Woods et al 2011;Geary et al 2015), despite investment in alternative approaches (Geary, 2012). The most successful paradigm in history has been to treat animals infected with parasites with experimental compounds and measure consequent changes in parasite burdens after necropsy.…”

Section: The Discovery Of Anthelmintics In the Futurementioning

confidence: 99%

Control of helminth ruminant infections by 2030

Charlier²,

et al. 2018

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Helminth infections have large negative impacts on production efficiency in ruminant farming systems worldwide, and their effective management is essential if livestock production is to increase to meet future human needs for dietary protein. The control of helminths relies heavily on routine use of chemotherapeutics, but this approach is unsustainable as resistance to anthelmintic drugs is widespread and increasing. At the same time, infection patterns are being altered by changes in climate, land-use and farming practices. Future farms will need to adopt more efficient, robust and sustainable control methods, integrating ongoing scientific advances. Here, we present a vision of helminth control in farmed ruminants by 2030, bringing to bear progress in: (1) diagnostic tools, (2) innovative control approaches based on vaccines and selective breeding, (3) anthelmintics, by sustainable use of existing products and potentially new compounds, and (4) rational integration of future control practices. In this review, we identify the technical advances that we believe will place new tools in the hands of animal health decision makers in 2030, to enhance their options for control and allow them to achieve a more integrated and sustainable approach to helminth control in support of animal welfare and production.

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Anthelmintic discovery and development in the animal health industry

Cited by 36 publications

References 31 publications

Polymorphism in ion channel genes of Dirofilaria immitis : Relevant knowledge for future anthelmintic drug design

Polymorphism in ion channel genes of Dirofilaria immitis : Relevant knowledge for future anthelmintic drug design

New WS9326A Congeners from Streptomyces sp. 9078 Inhibiting Brugia malayi Asparaginyl-tRNA Synthetase

Control of helminth ruminant infections by 2030

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