Taki et al (2021) have recently published the results obtained using wMicrotracker system for the discovery of new anthelmintic drugs. They’ve established a practical, cost-effective and semi-automated whole-worm high throughput screening (HTS) assay in a 384-well plate format which relies on the measurement of motility of larvae of Haemonchus contortus using infrared light-interference (wMicrotracker, Phylumtech).
Using this platform they were capable of screening ~10,000 compounds per week. They have screened a complete library of 80,500 small molecules and achieved a hit rate of 0.05%. They identified three small molecules that reproducibly inhibited larval motility and/or development (IC50 values of ~4 to 41 uM). Future work will assess the potential of selected hits as candidates for subsequent optimisation or repurposing against parasitic nematodes.
“This platform is practical, quantitative and semi-automated, and overcomes the limitations of our previous 96-well plate assay, achieving a = 10-times higher throughput and not requiring extensive technical skill to run or calibrate the assay”. Thus, this HTS assay is suited to the screening of libraries of tens of thousands to hundreds of thousands of compounds for subsequent hit-to-lead optimisation or effective repurposing and development. It costs about ~ USD 67,000 to set up; most of this expense relates to the purchase of a semi-automated liquid handling robot (at USD 30,000), two WMicroTracker ONE instruments (at USD 15,000 each) and a dissecting and a compound microscope (at USD 3000 each).
“The current assay should be adaptable to many socioeconomically important parasitic nematodes, including those that cause neglected tropical diseases (NTDs). This aspect is of relevance, given the goals of the World Health Organization (WHO) Roadmap for NTDs 2021–2030, to develop more effective drugs and drug combinations to improve patient outcomes and circumvent the ineffectiveness of some current anthelmintic drugs and possible drug resistance”.
Taki, Aya C., Joseph J. Byrne, Tao Wang, Brad E. Sleebs, Nghi Nguyen, Ross S. Hall, Pasi K. Korhonen, Bill C.H. Chang, Paul Jackson, Abdul Jabbar, and Robin B. Gasser.