Novel sources of therapeutic biomolecules : Isolating, characterising, and identifying antibacterial, antifungal, and antiviral compounds from Drosophila melanogaster

Dwarampudi, Venkata and Clancy, David (2025) Novel sources of therapeutic biomolecules : Isolating, characterising, and identifying antibacterial, antifungal, and antiviral compounds from Drosophila melanogaster. PhD thesis, Lancaster University.

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Abstract

In the search for untapped natural reservoirs of antimicrobials and antivirals; insects show great promise, providing viable alternatives to the current antibiotics in clinical use. This study explored Drosophila melanogaster as a source of small biomolecules with therapeutic potential, focusing on the antibacterial, antifungal, and antiviral properties of extracts produced from washing eggs and the surrounding food surfaces. Broad antimicrobial activity, found in the methanolic washes, was progressively fractionated, removing non-active components, leaving fractions containing molecules smaller than 800Da with comparable inhibitory activity as conventional antibiotics. The processing methods of, filtration, size exclusion chromatography (SEC) fractionation and HPLC-C18 reverse phase separations proved effective in isolating antibacterial, antifungal, and antiviral compounds. Two distinct regions of antibacterial activity were observed in the size exclusion fractionates, indicating the presence of two separate antibacterial molecules present in the extracts. Both molecules exhibited broad-spectrum activity against Gram (+) and Gram (-) strains with inhibitory effects against several antibiotic-resistant bacterial species. Refined egg washes also exhibited antifungal and antiviral activity; SEC fractionates demonstrated consistent inhibition of fungal growth and protection of cells against SARS-CoV-2. The antiviral fractions inhibited SARS-CoV-2 from lysing simian (mammalian) cells when conducting plaque assays and TCID50. HPLC fractionation of antiviral extracts indicated the conservation of antiviral activity following in-depth processing; however, more efficient HPLC throughputs with greater purity are required for more conclusive results. The mechanisms of action for all observed antimicrobials and antiviral effects are yet to be thoroughly explored and established, with the focus predominantly being on the purification and identification of the active molecules. The possibility of symbionts producing the molecules was explored, but this was beyond the scope of the research, highlighting other avenues of research. This study has proven the presence of active biomolecules from Drosophila melanogaster and their potential as a source of novel therapeutics.