Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Antiviral signaling, immune response and cell metabolism in human body are dysregulated by SARS-CoV-2, the causative agent of the COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While all four ORFs caused mitochondrial fragmentation and altered mitochondrial function, only ORF3a and ORF9c induced a marked structural alteration in mitochondrial cristae. ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes. In contrast, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes for proteins with critical mitochondrial functions and morphology. Genome-Scale Metabolic Models predicted common and private metabolic flux reprogramming, notably a depressed amino acid metabolism, and an enhanced metabolism of specific lipids distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.This research work was funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI+ Salud Global) (COVID-19-117 and SGL2103015), Junta de Andalucía (CV20-20089), Spanish Ministry of Science project (PID2021-123399OB-I00), the Agency for Management of University and Research Grants from Generalitat de Catalunya-AGAUR (2020PANDE00048 and 2021SGR00350) and ICREA foundation (ICREA-Academia-2021 to MC) of Generalitat de Catalunya, and an AESi grant of the Instituto de Salud Carlos III (PI20CIII-00014). TGG is recipient of a Ramón y Cajal contract funded by MCIN/AEU/10.13039/501100011033 and NextGeneration EU/PRTR.N

Inulin as a multifaceted (active)substance and its chemical functionalization: From plant extraction to applications in pharmacy, cosmetics and food

This review is aimed at critically discussing a collection of research papers on Inulin (INU)in different scientific fields. The first part of this work gives an overview on the main characteristics of native INU, including production, applications in food or cosmetics industries, its benefits on human health as well as its main nutraceutical properties. A particular focus is dedicated to the extraction techniques and to the specific effects of INU on intestinal microbiota. Other than in food industry, the number of INU applications increases dramatically in the pharmaceutical field especially due to its simple chemical functionalization. Thus, aim of this review is also to give practical examples of chemical functionalization performed on INU also by including critical comments based on the direct experience of the Authors. With this aim, a full paragraph is dedicated to practical chemical experiences useful to reduce the efforts when establishing new experimental conditions. Moreover, the pharmaceutical technology is also taken in special consideration by underlining the aspects leading at the preparation of formulations based on INU. At the end of the review, a critical paragraph is intended to feed the scientists’ curiosity on this versatile polysaccharide