Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Comparative Binding Study of Gliptins to Bacterial DPP4-like Enzymes for the Treatment of Type 2 Diabetes Mellitus (T2DM)

The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering increasing attention. Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, constitute a class of drugs extensively used in T2DM treatment. However, their potential interactions with gut microbiota remain poorly understood. In this study, we employed computational methodologies to investigate the binding affinities of various gliptins to DPP4-like homologs produced by intestinal bacteria. The 3D structures of DPP4 homologs from gut microbiota species, including Segatella copri, Phocaeicola vulgatus, Bacteroides uniformis, Parabacteroides merdae, and Alistipes sp., were predicted using computational modeling techniques. Subsequently, molecular dynamics simulations were conducted for 200 ns to ensure the stability of the predicted structures. Stable structures were then utilized to predict the binding interactions with known gliptins through molecular docking algorithms. Our results revealed binding similarities of gliptins toward bacterial DPP4 homologs compared to human DPP4. Specifically, certain gliptins exhibited similar binding scores to bacterial DPP4 homologs as they did with human DPP4, suggesting a potential interaction of these drugs with gut microbiota. These findings could help in understanding the interplay between gliptins and gut microbiota DPP4 homologs, considering the intricate relationship between the host metabolism and microbial communities in the gut

Supplemental information Comparative Binding Study of Gliptins to Bacterial DPP4-like Enzymes for the Treatment of Type 2 Diabetes Mellitus (T2DM)

Table S1.Comparative analysis of residues within binding pocket sections across 5 DPP4 homologs and the human variant. Colors visually represent aminoacids properties: pink indicates non-polar aliphatic residues, green represents polar uncharged residues, orange denotes aromatic R-groups, red signifies positively charged residues, and blue indicates negatively charged residues. Figure S1. 2D interaction maps of alogliptin predicted best pose with the six different DPP4 homologues studied. Figure S2. 2D interaction maps of linagliptin predicted best pose with the six different DPP4 homologues studied. Figure S3. 2D interaction maps of saxagliptin predicted best pose with the six different DPP4 homologues studied. Figure S4. 2D interaction maps of teneligliptin predicted best pose with the six different DPP4 homologues studied. Figure S5. 2D interaction maps of vildagliptin predicted best pose with the six different DPP4 homologues studied.Peer reviewe

MRGPRX2-mediated mast cell response to drugs used in perioperative procedures and anaesthesia

The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a β-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of β-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology