Challenges in natural product-based drug discovery assisted with in silico-based methods

The application of traditional medicine by humans for the treatment of ailments as well as improving the quality of life far outdates recorded history. To date, a significant percentage of humans, especially those living in developing/underprivileged communities still rely on traditional medicine for primary healthcare needs. In silico-based methods have been shown to play a pivotal role in modern pharmaceutical drug discovery processes. The application of these methods in identifying natural product (NP)-based hits has been successful. This is very much observed in many research set-ups that use rationally in silico-based methods in combination with experimental validation techniques. The combination has rendered the use of in silico-based approaches even more popular and successful in the investigation of NPs. However, identifying and proposing novel NP-based hits for experimental validation comes with several challenges such as the availability of compounds by suppliers, the huge task of separating pure compounds from complex mixtures, the quantity of samples available from the natural source to be tested, not to mention the potential ecological impact if the natural source is exhausted. Because most peer-reviewed publications are biased towards “positive results”, these challenges are generally not discussed in publications. In this review, we highlight and discuss these challenges. The idea is to give interested scientists in this field of research an idea of what they can come across or should be expecting as well as prompting them on how to avoid or fix these issues.