The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile.
In the Piedmont Basin (PB), one of the northernmost Mediterranean basins recording the Messinian Salinity Crisis (MSC), pollen and plant macroremains (leaves, fruits and seeds) were studied in four sedimentary sections of the post-evaporitic interval (5.6–5.33 Ma). The joint palaeobotanical investigations of the two datasets allowed the reconstruction of a floristic assemblage which consists of 133 taxa (95 woody and 38 non-woody taxa). The lowland/coastal vegetation reconstructed by integrating macro- and microfossil data exhibits several analogies with existing “types/formations” of South-Southeast Asia, whereas taxa occurring solely in the pollen record suggest the existence of altitudinal forests with conifers and a few angiosperms. We suggest that the generalized type of lowland, zonal palaeovegetation in the post-evaporitic Messinian of the PB was of no-analog type, but most similar to either “mixed mesophytic forests” or “broad-leaved evergreen forests”, which indicates a Köppen-Trewartha subtropical palaeoclimate.
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