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Bergna, A.

Publications and source records attributed to Bergna, A..

2 recordsLinked to original sources

In vitro Characterization of Peptidomimetic Proteolysis Targeting Chimera (PROTAC) as a Degrader of 3-Chymotrypsin-Like Protease (Mpro/3CLpro) against SARS-CoV-2

The SARS-CoV-2 main protease (3CLpro) is a key target for antiviral development. We investigated FT235, a peptidomimetic PROTAC linking a GC-376 warhead to pomalidomide for targeted degradation. FT235 bound 3CLpro, inhibiting activity (IC50 = 21.2 {micro}M), and reducing protease levels in cells. In vitro data showed no cytotoxicity up to 100 {micro}M and variant-dependent antiviral activity, with increased potency in the presence of a P-gp inhibitor. These results support PROTAC-based antivirals as promising therapeutic candidates.

microbiology↗

Unravelling native plant resistomes - The Sphagnum microbiome harbours versatile and novel antimicrobial resistance genes

The expanding antibiotic resistance crisis calls for a more in depth understanding of the importance of antimicrobial resistance genes (ARGs) in pristine environments. We, therefore, studied the microbiota associated with Sphagnum forming the main vegetation in undomesticated, evolutionary old bog ecosystems. In our complementary analysis of a culture collection, metagenomic data and a fosmid library, we identified a low abundant but highly diverse pool of resistance determinants, which targets an unexpected broad range of antibiotics including natural and synthetic compounds. This derives both, from the extraordinarily high abundance of efflux pumps (80%), and the unexpectedly versatile set of ARGs underlying all major resistance mechanisms. The overall target spectrum of detected resistance determinants spans 21 antibiotic classes, whereby {beta}-lactamases and vancomycin resistance appeared as the predominant resistances in all screenings. Multi-resistance was frequently observed among bacterial isolates, e.g. in Serratia, Pandorea, Paraburkhotderia and Rouxiella. In a search for novel ARGs we identified the new class A {beta}-lactamase Mm3. The native Sphagnum resistome comprising a highly diversified and partially novel set of ARGs contributes to the bog ecosystems plasticity. Our results shed light onto the antibiotic resistance background of non-agricultural plants and highlight the ecological link between natural and clinically relevant resistomes.

microbiology↗