ABSTRACT
Natural products have a significant role in drug discovery. Their unique chemical structures have led to compounds in clinical use to treat different diseases. Also, natural products are significant sources of inspiration or starting points to develop new therapeutic agents. There are also unique natural products such as peptides and macrocycles that offer sources or starting points to address complex diseases. Computational approaches that used chemoinformatics and molecular modeling methods contribute to assisting and accelerating natural product-based drug discovery. Several research groups have recently used computational methodologies to organize data, interpret results, generate and test hypotheses, filter large chemical databases before the experimental screening, and design experiments. Herein, we discuss chemoinformatics and molecular modeling applications to uncover bioactive natural products. We also discuss in silico methods to optimize the biological activity and anticipate potential toxicity issues of natural products. As case studies, we discuss the role of natural products for COVID-19 drug discovery and their impact on the identification of compounds with activity against DNA methyltransferase, an epigenetic target with relevance in cancer and other diseases. © 2022 Elsevier Inc. All rights reserved.