Applications of molecular docking in natural products-based drug discovery

Natural products have a long history of use in the treatment of various diseases particularly in developing countries. The use of compounds of natural origin as lead compounds for the development of conventional drugs is widely recognised. Natural product-based drug discovery efforts in developing countries mostly involve the use of crude extracts in in-vitro and/or in-vivo assays. There are limited efforts at isolating active principles for structure elucidation studies. Studies that isolate pure secondary metabolites and characterize their structures have limited bioactivity evaluations. In conventional drug discovery programs, molecular docking serves as a useful tool for predicting interactions of small molecules with drug target(s) to guide synthesis decisions. Medicinal chemists use this tool to predict and synthesize compounds likely to have pharmacological activity and thus save time and cost for drug discovery. Efforts have been made to incorporate molecular docking techniques into natural products-based drug discovery. The objective of this review is to discuss molecular docking in natural product drug discovery programs with the goal of providing easy-to-understand information to help beginners interested in incorporating molecular docking in their research. This is expected to enhance natural product screening programs by predicting which phytochemicals are likely to show success, especially in new disease situations such as COVID-19. Applications in the repositioning of plants for emerging conditions are also discussed.