The plant microbiome is pivotal to sustainable agriculture and global food security, yet some challenges hinder fully harnessing it for field-scale impact. These challenges span measurement and integration, ecological predictability and translation across environments and seasons. Key obstacles include technical challenges, notably overcoming the limits of current sequencing for low-abundance taxa and whole-community coverage, integrating multi-omics data to uncover functional traits, addressing spatiotemporal variability in microbial dynamics, deciphering the interplay between plant genotypes and microbial communities, and enforcing standardized controls, metadata, depth targets and reproducible workflows. The rise of synthetic biology, omics tools, and artificial intelligence offers promising avenues for engineering plant–microbe interactions, yet their adoption requires regulatory, ethical, and scalability issues alongside clear economic viability for end-users and explicit accounting for evolutionary dynamics, including microbial adaptation and horizontal gene transfer to ensure durability. Furthermore, there is a need to translate research findings into field-ready applications that are validated across various soils, genotypes, and climates, while ensuring that advances benefit diverse regions through global, interdisciplinary collaboration, fair access, and benefit-sharing. Therefore, this review synthesizes current barriers and promising experimental and computational strategies to advance plant microbiome research. Consequently, a roadmap for fostering resilient, climate-smart, and resource-efficient agricultural systems focused on benchmarked, field-validated workflows is proposed.

Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria commonly colonize plant tissues such as stems, roots, and leaves, seed-associated endophytes generally exhibit lower diversity compared to those in other plant compartments. Nevertheless, seed-borne microbes are of particular importance, as they represent the initial microbial inoculum that influences a plant’s critical early developmental stages. The seed endophytic microbiome is of particular interest due to its potential for vertical transmission and its capacity to produce a broad array of phytohormones, enzymes, antimicrobial compounds, and other secondary metabolites. Collectively, these functions contribute to enhanced plant biomass and yield, especially under abiotic and biotic stress conditions. Despite their multifaceted roles, seed microbiomes remain underexplored in plant ecology, and their potential benefits are not yet fully understood. This review highlights recent advances in our understanding of the diversity, community composition, mechanisms of action, and agricultural significance of seed endophytic microbes. Furthermore, it synthesizes current insights into how seed endophytes promote plant health and productivity and proposes future research directions to fully harness their potential in sustainable agriculture.

Momordica spp. has been traditionally used to manage type 2 diabetes mellitus, but the mechanisms and metabolites remain unclear. This study evaluated the inhibitory potential of Momordica balsamina extracts on α-amylase and α-glucosidase in vitro, identifying cucurbitacin I and momordin Ic via high-performance liquid chromatography-photo diode array, and their inhibitory potential in silico. Ethyl acetate seed extract (14.46 µg/ml) and hexane fruit flesh extract (16.79 µg/ml) exhibited lower IC₅₀ values against α-amylase and α-glucosidase, respectively, compared to acarbose (reference standard). Comparatively, momordin Ic concentrations (36.57-605.98 µg/ml) were higher than cucurbitacin I (17.08-44.34 µg/ml). A 140 ns simulation showed that cucurbitacin I (-63.06 kcal/mol) and momordin Ic (-66.53 kcal/mol) exhibited stronger binding to α-amylase than acarbose (-36.46 kcal/mol), whereas cucurbitacin I (-38.08 kcal/mol) and momordin Ic (-54.87 kcal/mol) displayed weaker binding to α-glucosidase, relative to acarbose (-63.73 kcal/mol). Generally, momordin Ic demonstrated better thermodynamic properties, hence further in vitro and in vivo studies are needed to validate their antidiabetic potential.

The COVID‐19 pandemic highlighted the role of rapid viral mutation and global connectivity in accelerating viral emergence and spread, emphasising the necessity for expedited and adaptable antiviral drug discovery and development. Despite ongoing efforts to develop effective, low‐toxicity therapeutics, the number of antivirals that have achieved clinical approval remains limited. The shortfall is especially significant in developing countries, where access to new antivirals is limited by high prices, few options, import dependence, unstable supply chains and weak purchasing systems. The challenge is further heightened by the emergence of increasingly drug‐resistant variants while vaccines often provide inadequate protection against newly mutated or novel viruses. Consequently, the identification of novel antiviral agents that are both effective and cost‐efficient via innovative strategies for antiviral drug discovery is essential to manage and control viral infections. Therefore, this review examines the different challenges associated with conventional antiviral drugs alongside recent strategies in antiviral drug discovery and development, such as the exploitation of plant secondary metabolites with antiviral properties, advanced microscopy technologies, computer‐aided drug design, artificial intelligence and machine learning, gene‐editing technologies, drug combination therapy and nanotechnology‐enhanced drug delivery systems. Additionally, this study proposes a simple decision‐focused pathway integrating natural products, computation and targeted delivery to guide candidate prioritisation, optimisation and translation from discovery to implementation. While these emerging strategies offer considerable promise, challenges related to validation, toxicity, scalability and equitable access remain important considerations for successful clinical translation. Future research should therefore integrate complementary technologies to accelerate the development of effective antiviral agents against current and emerging viral threats.

Background: In rural areas of KwaZulu-Natal and Eastern Cape Provinces, South Africa, women have traditionally used bark extracts from Cassipourea flanaganii, C. malosana, and C. gummiflua for skin lightening and sun protection. This study investigates the anti-tyrosinase and antioxidant activities of methanolic bark extracts from these species, aiming to validate their traditional use and identify potential lead compounds for the treatment of skin hyperpigmentation. Methods: Anti-tyrosinase activity was evaluated using half-maximal inhibitory concentration (IC₅₀) values, and antioxidant capacity was measured through FRAP, DPPH, and TEAC assays. Polyphenol and flavanol contents were quantified using Folin-Ciocalteu method. Potential lead compounds were identified through molecular docking, pharmacokinetic analysis, and molecular dynamics (MD) simulations. Statistical analyses, including ANOVA and post-hoc tests, compared extract activities. Results: C. flanaganii exhibited the most potent anti-tyrosinase activity (IC₅₀: 37.10 μg/mL), though statistical differences among species were non-significant. C. gummiflua showed the highest polyphenol (143.68 mg GAE/g) and flavanol (14.67 mg QE/g) content, correlating with superior antioxidant activity (FRAP: 526.07 μmol AAE/g; DPPH: 390.26 μmol TE/g; TEAC: 596.98 μmol TE/g). The isolated compound 7-methoxygeranin A demonstrated lower anti-tyrosinase activity (IC₅₀: 45.16 μg/mL) compared to C. flanaganii extract, suggesting the presence of more potent metabolites. Molecular docking and MD simulations identified emodin 6,8-dimethyl ether as a thermodynamically stable lead compound (binding free energy: − 39.88 kcal/mol), interacting with key catalytic residues over 150 ns. The compound demonstrated prolonged residence at the active site of tyrosinase, indicating strong-binding stability. Conclusion: While C. flanaganii demonstrated the strongest anti-tyrosinase activity, C. gummiflua showed the highest antioxidant potential. Emodin 6,8-dimethyl ether emerged as a promising candidate for skin-lightening applications, warranting further in vitro and in vivo validation. These findings support the traditional use of Cassipourea species and highlight their potential for developing natural skin health products. Further studies are needed to explore the pharmacokinetics, safety, and efficacy of these compounds in clinical settings.