Neglected tropical diseases (NTDs) cause enormous suffering, morbidity, and significant numbers of deaths. Globally billion people suffer from them and for those termed tool-ready NTDs, the recommended control strategy is mass drug administration (MDA) with drugs and others including Buruli ulcer prolonged treatment with antibiotics, additionally, no vaccines are commercially available. We are concerned the current drugs have been used extensively for long periods, which will lead to reduced efficacies and/or resistance in the long term. The conventional approaches to drug discovery are very challenging, expensive, and time-consuming processes, need several hands and take approximately 15 years to get approval. It is also characterized by a low rate of therapeutic discovery, which in some cases involves bioprospecting. Moreover, the number of approved drugs is steadily declining because of these challenges, with toxicity accounting for approximately one-third of withdrawals and the rest mostly due to early-stage terminations that are related to suboptimal efficacy and safety issues. In-silico approaches will overcome most of these research and development (R&D) challenges by reducing costs.