Schistosomes: challenges in compound screening

TLDR

Schistosome biology has progressed since the 1960s with successful laboratory cultivation of life‑cycle stages, enabling in‑vitro studies of growth, development, and pathogenic mechanisms and the development of diagnostic, immunological, and chemotherapeutic targets, while chemotherapeutic control remains the mainstay but resistance to the sole drug praziquantel is a growing concern. This paper reviews the current state of in‑vitro and in‑vivo drug screening strategies against schist.

Abstract

Major progress in studying the biology of schistosomes had been achieved since the late 1960s with the successful laboratory cultivation of the parasite's life cycle stages in the vertebrate (in vivo animal models) and snail hosts. This was followed by establishment of in vitro culture techniques for cultivation of the different life cycle stages to understand the mechanisms regulating the parasite's growth, development, transformation, pathogenicity and survival, with prospects to develop and identify relevant candidate diagnostic, immunological and chemotherapeutic targets. Chemotherapeutic measures have been the mainstay in the control of schistosomiasis. The use of praziquantel, a relatively safe and orally administered drug, in targeted or mass treatment programmes had significantly reduced the prevalence of schistosomiasis in disease-endemic countries. However, with only one drug of choice for treatment, parasite resistance remains a major concern. Thus, new drug discovery against schistosomes cannot be overemphasised. Undoubtedly, this will require an integrated system that includes not only rational chemical synthesis and lead optimisation, but also appropriate drug screening strategies. This paper reviews the present state of in vitro and in vivo drug screening strategies against schistosomes. It also highlights the best practices for compound screening in the TDR-designated compound screening centres and details some of the challenges involved in in vitro and in vivo compound screening.