Anthelmintic drug discovery: target identification, screening methods and the role of open science.

Frederick A Partridge,Graham M Wynne,David B Sattelle,Kathryn J Else,Marina Nick,Carole J R Bataille,Angela J Russell,Angela J Russell,Ruth Forman

doi:10.3762/bjoc.16.105

Frederick A Partridge, Graham M Wynne + Show 7 more

Open Access

https://doi.org/10.3762/bjoc.16.105

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Abstract

Helminths, including cestodes, nematodes and trematodes, are a huge global health burden, infecting hundreds of millions of people. In many cases, existing drugs such as benzimidazoles, diethylcarbamazine, ivermectin and praziquantel are insufficiently efficacious, contraindicated in some populations, or at risk of the development of resistance, thereby impeding progress towards World Health Organization goals to control or eliminate these neglected tropical diseases. However, there has been limited recent progress in developing new drugs for these diseases due to lack of commercial attractiveness, leading to the introduction of novel, more efficient models for drug innovation that attempt to reduce the cost of research and development. Open science aims to achieve this by encouraging collaboration and the sharing of data and resources between organisations. In this review we discuss how open science has been applied to anthelmintic drug discovery. Open resources, including genomic information from many parasites, are enabling the identification of targets for new antiparasitic agents. Phenotypic screening remains important, and there has been much progress in open-source systems for compound screening with parasites, including motility assays but also high content assays with more detailed investigation of helminth physiology. Distributed open science compound screening programs, such as the Medicines for Malaria Venture Pathogen Box, have been successful at facilitating screening in diverse assays against many different parasite pathogens and models. Of the compounds identified so far in these screens, tolfenpyrad, a repurposed insecticide, shows significant promise and there has been much progress in creating more potent and selective derivatives. This work exemplifies how open science approaches can catalyse drug discovery against neglected diseases.

Highlights

Anthelmintic drugs is the collective term for the group of drugs which treat infections of animals or humans infected with parasitic worms
The current review focusses on the unmet need in anthelmintic drug discovery to tackle the burden of human helminth infections, infection of livestock with parasitic worms has important animal welfare implications and can result in considerable economic losses to the livestock industry
The World Health Organization (WHO) recommends annual or biannual intervention with the anthelmintics albendazole (ALB, 1) or mebendazole (MEB, 2), to treat STHs [25,26]

Summary

Introduction

Anthelmintic drugs is the collective term for the group of drugs which treat infections of animals or humans infected with parasitic worms (helminths). Parasitic worms infect a wide range of species and as such present a major burden on human health, and livestock production and crop production. The current review focusses on the unmet need in anthelmintic drug discovery to tackle the burden of human helminth infections, infection of livestock with parasitic worms has important animal welfare implications and can result in considerable economic losses to the livestock industry. The most common infections, which we will highlight in this review, are caused by soil transmitted helminths (STHs), schistosomes and lymphatic filarial worms (Table 1). These disease main etiologic helminth number infected (million). Infections (due in part to size and number of worms) and intestinal blockages (potentially requiring surgery), growth stunting and effects on cognition [10,11,12]

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