Integrated solutions to climate change, resource scarcity, environmental degradation, food waste management, and an increasing demand for food are essential for the future of food and agriculture. In this sense, new products and strategies based on the reuse of environmentally sustainable materials are increasingly emerging, while technologies can broaden the scope of intervention, facilitating and accelerating the development of waste-free food systems.

Wine production reached 260 mhL (excluding juices and musts) in 2020 [1], generating a large amount of wastes. Traditionally, grape byproducts have been used as fertilizers and/or biomass. In recent years, however, they have been proposed as an interesting source of bioactive compounds that could be used for several applications [2].Pomace from red grapes, one of the main winemaking wastes, contains phenolic compounds such as anthocyanidins, catechins, proanthocyanidins, tannins and organic acids with proven antiviral activity [3]. For instance, it has been reported that compounds of wine and its byproducts can inactivate viruses such as herpes simplex (HSV) type 1 and enteric viruses [4,5,6]. In addition, several studies have focused on the mechanisms of action of these bioactive compounds, demonstrating that these molecules can inhibit adsorption, as well as virus binding and virus entry, integrase, RTase and protease. In addition, they act on the inhibition of replication of DNA and RNA polymerases as well as the formation of protein complexes [7].Hence, opportunities to reduce food waste and integrate this approach to the entire supply chain and reap the beneficial properties of these bioactive compounds are required. In this sense, the use of new ingredients for pollinators, as proposed in this study, could be a potential alternative for food waste reduction. Similar results were found in a study where they pointed out that there was a response in the genes involved in detoxification in bees fed with sucrose solution enriched by phenolic compounds [8].The honeybee (Apis mellifera L.) is an important species with a key role in agriculture as a pollinator of plant species. Honeybees are involved in enhancing the biodiversity of agricultural and non-agricultural systems [9]. Therefore, honeybee losses have become a matter of increasing concern worldwide. Deformed wing virus (DWV), which is a widespread virus associated with the spread of the Varroa destructor mite, is considered as one of the most critical factors contributing to bee losses at the global level [10]. The virus causes physical malformations in wings, abdominal swelling, paralysis, and behavioral disturbances in bees. In addition, studies have reported that DWV infection can alter the molecular mechanisms of learning, affecting memorization ability and disrupting the central and peripheral nervous systems [11]. DWV transmission follows several routes, with varying pathogen loads and virulence. This transmission of the virus (DWV) in A. mellifera colonies can occur in two ways. On the one hand, it can be transmitted vertically (from the queen or drone to the offspring). On the other hand, it can be transmitted horizontally through either shared food resources or via trophallaxis [12]. Consequently, viral diseases have demonstrated a negative impact on food security, wildlife and economic stability [13].Currently, beekeepers have several tools to control the vector of DWV, the Varroa mite. Among the measures, the use of synthetic chemical acaricides or natural repellents, such as essential oils, organic acids and a combination of the use of management practices are included, although they are not sufficiently effective [14]. Moreover, treatments for DWV are focused on vector control, but there is no curative treatment for colonies with high viral loads.Biotic and abiotic factors are key contributors to colony health and survival (e.g., the diet of the colony), constituting alternatives to controlling DWV. It has been demonstrated that greater DWV levels are related to the consumption of a poor-quality diet (e.g., sugar water). Nevertheless, bees fed higher-quality food, for instance pollen-containing diets, present low DWV levels [15]. Phytochemicals, particularly phenolics, terpenoids and alkaloids, present antimicrobial activity [16] and even protect against microbial alterations in bees. Recently, researchers have described the antiviral activity of mycelium extracts, specifically of multiple polypore fungal species. In fact, [17] they found that the health of honeybees was enhanced after feeding water was enriched with a fungi source and their antimicrobial compounds, considering this situation to be self-medication. In addition, it has been reported that levels of DWV decreased up to 500-fold when a syrup of sugar and thymol, a monoterpene isolated from thyme, was used as food for young bees and it was released into field colonies [18]. With respect to phenolic compounds, the methanolic extracts from Chilean native plant leaves such as Ugni molinae, Gevuina avellana and Aristotelia chilensis were evaluated on the load of N. ceranae, seeking biological activity [19]. The authors concluded that leaf extracts, with high concentrations of rutin and myricetin, and propolis with high concentrations of galangin and pinocembrin, presented antiparasitic and antimicrobial activity. In addition, they proved an improved survival of bees and a decreased load of N. ceranae in infected bees and described some of the mechanisms involved in the enhanced immune system response of honeybees by the action of the phytochemicals.Honeybees are endowed with an RNA interference (RNAi) molecular machinery and a eukaryotic antiviral immune system [20]. The main pathway of the antiviral defense mechanism in insects is mediated by the small interfering RNA (siRNA) belonging to a post-transcriptional, sequence-specific, gene silencing mechanism [21]. This RNAi could be induced by feeding or injecting dsRNA as an alternative to prevent gene expression and, consequently, block the replication of RNA viruses, including DWV [22,23]. As with other insects, honeybee antiviral responses also include apoptosis, eicosanoid biosynthesis, autophagy, melanization and endocytosis. Furthermore, Toll, NF-κB (Nuclear Factor κB), JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription), JNK (c-Jun N-terminal kinase), and MAPK (Mitogen-Activated Protein Kinases) pathways are found [24].Consequently, grape wastes, specifically grape pomace, which is rich in phenolic compounds, could be formulated as a supplement, enhancing the honeybee immune system. In order to protect bioactive compounds obtained from grape waste and avoid their degradation over time, encapsulation techniques have been developed to ensure their stability. Among them, spray drying has been used widely in the encapsulation to large-scale production since it is economical and adaptable, while it makes a product of excellent quality. The process generates stability and protection to the bioactive compounds by acting as a physical barrier and allowing for slow release. Concerning the loss of bioactive content, the high temperature in the process is the main issue, and thus the process needs to be optimized, while the properties and bioactivity of the final ingredient should be studied [25]. Studies carried out with Tintorera have shown that the use of this technique preserves anthocyanin content by maintaining the formulation for four weeks [26]. The authors demonstrated that after spray drying, the ingredient had an adequate anthocyanin encapsulation efficiency, resulting in increased stability and bioaccessibility.

The use of environmentally friendly alternatives to help mitigate phytosanitary problems in apicultural systems and the reuse of winemaking waste is worthy for environmental sustainability and food security. Therefore, the objective of this research was to evaluate the effects of grape pomace powder as a dietary supplement to enhance the immune system of honeybees affected by DWV.