The most common pasteurisation method used by human milk banks is Holder pasteurisation. This involves thermal processing, which can denature important proteins and can potentially reduce the natural antimicrobial properties found in human milk. This study assesses the application of a hybrid method comprised of freeze-drying followed by low-dose gamma-irradiation for nonthermal donor human milk pasteurisation. Freeze-drying donor human milk followed by gamma-irradiation at 2 kGy was as efficient as Holder pasteurisation in the reduction of bacterial inoculants of Staphylococcus aureus (106 cfu/mL) and Salmonella typhimurium (106 cfu/mL) in growth inhibition assays. These assays also demonstrated that human milk naturally inhibits the growth of bacterial inoculants S. aureus, S. typhimurium, and Escherichia coli. Freeze drying (without gamma-irradiation) did not significantly reduce this natural growth inhibition. By contrast, Holder pasteurisation significantly reduced the milk’s natural antimicrobial effect on S. aureus growth after 6 h (−19.8% p = 0.01). Freeze-dried and then gamma-irradiated donor human milk showed a strong antimicrobial effect across a dose range of 2–50 kGy, with only a minimal growth of S. aureus observed after 6 h incubation. Thus, a hybrid method of freeze-drying followed by 2 kGy of gamma-irradiation preserves antimicrobial properties and enables bulk pasteurisation within sealed packaging of powderised donor human milk. This work forwards a goal of increasing shelf life and simplifying storage and transportation, while also preserving functionality and antimicrobial properties.
Herpes simplex virus (HSV) infections are a worldwide health problem in need of new effective treatments. Of particular interest is the identification of antiviral agents that act via different mechanisms compared to current drugs, as these could interact synergistically with first-line antiherpetic agents to accelerate the resolution of HSV-1-associated lesions. For this study, we applied a structure-based molecular docking approach targeting the nectin-1 and herpesvirus entry mediator (HVEM) binding interfaces of the viral glycoprotein D (gD). More than 527,000 natural compounds were virtually screened using Autodock Vina and then filtered for favorable ADMET profiles. Eight top hits were evaluated experimentally in African green monkey kidney cell line (VERO) cells, which yielded two compounds with potential antiherpetic activity. One active compound (1-(1-benzofuran-2-yl)-2-[(5Z)-2H,6H,7H,8H-[1,3] dioxolo[4,5-g]isoquinoline-5-ylidene]ethenone) showed weak but significant antiviral activity. Although less potent than antiherpetic agents, such as acyclovir, it acted at the viral inactivation stage in a dose-dependent manner, suggesting a novel mode of action. These results highlight the feasibility of in silico approaches for identifying new antiviral compounds, which may be further optimized by medicinal chemistry approaches.
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