A systematic review to understand the current scenarios employing plants and their secondary metabolites as antifungal agents: opportunities and challenges

Abstract

Fungal diseases consistently affect the health of plants, humans, and animals, diminishing output. About 70% of major crop diseases are caused by fungi, causing economic losses and food security risks. Human invasive fungal infections have increased dramatically in recent decades, with substantial death rates. Antibiotic resistance, a global issue, makes fungal infections difficult to treat. Thus, alternative and sustainable fungal disease management strategies are needed immediately. As potential antifungal medications, antifungal plants and their secondary metabolites are of interest. This review aims to leverage the existing knowledge about the key plant secondary metabolites with antifungal potential, classify their mechanisms of action, and explore formulation strategies and computational tools to overcome current therapeutic limitations to curb the loss due to fungal diseases and to provide a platform for researchers to work on this area. The literature survey was conducted using the databases Google Scholar, ScienceDirect, and PubMed, adhering to the PRISMA guidelines. The study examines 340 scholarly papers from 1990 to mid-2023. The study identified 648 plant species whose 268 secondary metabolites have shown antifungal activity in vitro, in vivo, and in silico. However, considering the vast diversity of plant species on Earth, only a small fraction of them and their secondary metabolites have been studied. Despite the plant's antifungal properties, its mode of action and bioactive components are often unknown. Moreover, the synergistic or co-potentiation effects of secondary metabolites in crude extracts have been scarcely explored. In silico investigations are limited by fungal target molecular structures, emphasizing the need for target purity and structural elucidation. In conclusion, phytochemicals can treat fungal illnesses naturally. Their diverse modes of action and broad antifungal characteristics make them promising research subjects.