Historically, natural products (NPs) have been the largest source of inspiration for the design of new drugs. In recent years (2018 compared to 2006), there has been a significant increase in the number of NP-based drugs. The recent technological advances, especially in the artificial intelligence (AI) and chemoinformatics areas, have boosted the computer-aided drug design (CADD) NP-based. Among the recent progress in AI, the development of machine learning models to predict the target proteins of natural products stands out. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic outbreak, the CAAD NP-based represented a main approach in the design and identification of lead compounds against the virus. Natural product (NP) databases are crucial tools for the CADD, since they provide access to thousands of molecules.