Microplastics are readily available in the natural environment. Due to the pervasiveness of microplastic pollution, its effects on living organisms necessitate further investigation. The size, time of exposure, and amount of microplastic particles appear to be the most essential factor in determining their toxicological effects, either organismal or sub-organismal. For our research work, we preferred to work on a terrestrial model organism Drosophila melanogaster (Oregon R⁺). Therefore, in the present study, we characterized 2–100 µm size PET microplastic and confirmed its accumulation in Drosophila, which allowed us to proceed further in our research work. At larger dosages, research on locomotory activities such as climbing, jumping, and crawling indicated a decline in physiological and neuromuscular functions. Our studies also determined retarded development in flies and decreased survival rate in female flies after exposure to the highest concentration of microplastics. These experimental findings provide insight into the possible potential neurotoxic effects of microplastics and their detrimental effects on the development and growth of flies.

NUDIX hydrolase 5 (NUDT5) is an enzyme involved in the hydrolysis of nucleoside diphosphates linked to other moieties, such as ADP-ribose. This cofactor is vital in redox reactions and is essential for the activity of sirtuins and poly(ADP-ribose) polymerases, which are involved in DNA repair and genomic stability. It has been shown that NUDT5 activity can also influence NAD+ homeostasis, thereby affecting cancer cell metabolism and survival. In this regard, the discovery of NUDT5 inhibitors has emerged as a potential therapeutic approach in cancer treatment. In this study, we conducted a high-throughput virtual screening of marine bacterial compounds against the NUDT5 enzyme and four molecules were selected based on their docking scores. These compounds established strong interactions within the NUDT5 active site, with molecular analysis highlighting the key role of Trp^28A and Trp^46B residues. Molecular dynamics simulations over 200 ns indicated a stable behavior, in association with root mean square deviation values always below 3 Å, suggesting conformational stability. Free energy landscape analysis further supported their potential as NUDT5 inhibitors, offering avenues for novel therapeutic strategies against NUDT5-associated breast cancer.