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Buch, I.

Publications and source records attributed to Buch, I..

2 recordsLinked to original sources

The worldwide invasion of Drosophila suzukii isaccompanied by a large increase of transposable elementload and a small number of putatively adaptive insertions

Transposable Elements (TEs) are ubiquitous and mobile repeated sequences. They are major determinants of host fitness. Here, we portrayed the TE content of the spotted wing fly Drosophila suzukii. Using a recently improved genome assembly, we reconstructed TE sequences de novo, and found that TEs occupy 47% of the genome and are mostly located in gene poor regions. The majority of TE insertions segregate at low frequencies, indicating a recent and probably ongoing TE activity. To explore TE dynamics in the context of biological invasions, we studied variation of TE abundance in genomic data from 16 invasive and six native populations (of D. suzukii). We found a large increase of the TE load in invasive populations correlated with a reduced Watterson estimate of genetic diversity [Formula] a proxy of effective population size. We did not find any correlation between TE contents and bio-climatic variables, indicating a minor effect of environmentally induced TE activity. A genome-wide association study revealed that ca. 5,000 genomic regions are associated with TE abundance. We did not find, however, any evidence in such regions of an enrichment for genes known to interact with TE activity (e.g. transcription factor encoding genes or genes of the piRNA pathway). Finally, the study of TE insertion frequencies revealed 15 putatively adaptive TE insertions, six of them being likely associated with the recent invasion history of the species.

evolutionary biology↗

Conserved interactions required for in vitro inhibition of the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

The COVID-19 pandemic caused by the SARS-CoV-2 requires a fast development of antiviral drugs. SARS-CoV-2 viral main protease (Mpro, also called 3C-like protease, 3CLpro) is a potential target for drug design. Crystal and co-crystal structures of the SARS-CoV-2 Mpro have been solved, enabling the rational design of inhibitory compounds. In this study we analyzed the available SARS-CoV-2 and the highly similar SARS-CoV-1 crystal structures. We identified within the active site of the Mpro, in addition to the inhibitory ligands interaction with the catalytic C145, two key H-bond interactions with the conserved H163 and E166 residues. Both H-bond interactions are present in almost all co-crystals and are likely to occur also during the viral polypeptide cleavage process as suggested from docking of the Mpro cleavage recognition sequence. We screened in silico a library of 6,900 FDA-approved drugs (ChEMBL) and filtered using these key interactions and selected 29 non-covalent compounds predicted to bind to the protease. Additional screen, using DOCKovalent was carried out on DrugBank library (11,414 experimental and approved drugs) and resulted in 6 covalent compounds. The selected compounds from both screens were tested in vitro by a protease activity inhibition assay. Two compounds showed activity at the 50M concentration range. Our analysis and findings can facilitate and focus the development of highly potent inhibitors against SARS-CoV-2 infection.

microbiology↗