A Focus on Natural Autophagy Modulators as Potential Host-Directed Weapons Against Emerging and Re-Emerging Viruses

Autophagy is a highly conserved intracellular process involved in maintaining homeostasis and in the degradation of damaged organelles and external pathogens. Nature provides complex and varied reservoirs of scaffolds and chemical entities that may have a pivotal role in the search for new therapeutic leads. Among them, phytocompounds have been amply exploited in the search for new autophagy modulators to tackle diseases like cancer and degenerative disorders, while their use as potential antiviral agents has been explored to a limited extent. The modulation of autophagy in viral infections may play a dual and contraposing role. Depending on the replication mechanism of the virus, it may serve as an adjuvant in the innate immune response of the host, or it may be hijacked by viruses, favoring their replication. This review is intended to present an overview of antiviral natural compounds and extracts capable of modulating autophagy, and it seeks to provide a solid foundation for researchers to further investigate the mechanisms of autophagy modulation during viral infections and to identify diverse molecular entities for antiviral drug discovery.