Discovery of 3-oxo-1,2,3,4-tetrahydropyrido[1,2-a]pyrazin derivatives as SARS-CoV-2 main protease inhibitors through virtual screening and biological evaluation.

The COVID-19 caused by SARS-CoV-2 has led to a global pandemic that continues to impact societies and economies worldwide. The main protease (Mpro) plays a crucial role in SARS-CoV-2 replication and is an attractive target for anti-SARS-CoV-2 drug discovery. Herein, we report a series of 3-oxo-1,2,3,4-tetrahydropyrido[1,2-a]pyrazin derivatives as non-peptidomimetic inhibitors targeting SARS-CoV-2 Mpro through structure-based virtual screening and biological evaluation. Further similarity search and structure-activity relationship study led to the identification of compound M56-S2 with the enzymatic IC50 value of 4.0 µM. Moreover, the molecular simulation and predicted ADMET properties, indicated that non-peptidomimetic inhibitor M56-S2 might serve as a useful starting point for the further discovery of highly potent inhibitors targeting SARS-CoV-2 Mpro.

Plant diversity is more important than soil microbial diversity in explaining soil multifunctionality in Qinghai-Tibetan plateau wetlands.

The Qinghai-Tibetan Plateau harbors rich and diverse wetlands that provide multiple ecological functions simultaneously. Although the relationships between biodiversity and wetland functioning have been well studied in recent decades, the links between the multiple features of plant and microbial communities and soil multifunctionality (SMF) remain unknown in the high-altitude wetlands that are extremely sensitive to human disturbance. Here, using the single function, averaging, weighted, and multiple-threshold methods, we calculated the SMF of Qinghai-Tibetan wetlands based on 15 variables associated with soil nutrient status, nutrient cycle, and greenhouse gas emission. We then related SMF to multidimensional (species, phylogenetic, and functional) diversity of plants and soil microorganisms and microbial network modules. The results showed that plant diversity explained more variance in SMF than soil microbial diversity, and plant species richness and phylogenetic distance were positive predictors of SMF. Bacterial network modules were more positively related to SMF than fungal network modules, and the alpha diversity of bacterial network modules contributed more to SMF than the diversity of the whole bacterial community. Pediococcus, Hirsutella, and Rhodotorula were biomarkers for SMF and had significant relationships with nitrogen mineralization and greenhouse gas emissions. Together, these results highlight the importance of plant diversity and bacterial network modules in determining the SMF, which are crucial to predicting the response of ecosystem functioning to biodiversity loss under intensifying anthropogenic activities.

Dioxygen compatible electron donor-acceptor catalytic system and its enabled aerobic oxygenation.

The photochemical properties of Electron Donor-Acceptor (EDA) complexes present exciting opportunities for synthetic chemistry. However, these strategies often require an inert atmosphere to maintain high efficiency. Herein, we develop an EDA complex photocatalytic system through rational design, which overcomes the oxygen-sensitive limitation of traditional EDA photocatalytic systems and enables aerobic oxygenation reactions through dioxygen activation. The mild oxidation system transfers electrons from the donor to the effective catalytic acceptor upon visible light irradiation, which are subsequently captured by molecular oxygen to form the superoxide radical ion, as demonstrated by the specific fluorescent probe, dihydroethidine (DHE). Furthermore, this visible-light mediated oxidative EDA protocol is successfully applied in the aerobic oxygenation of boronic acids. We believe that this photochemical dioxygen activation strategy enabled by EDA complex not only provides a practical approach to aerobic oxygenation but also promotes the design and application of EDA photocatalysis under ambient conditions.

Linking ecosystem multifunctionality to microbial community features in rivers along a latitudinal gradient.

Microorganisms regulate numerous ecosystem functions and show considerable differences along a latitudinal gradient. Although studies have revealed the latitudinal patterns of microbial community structure and single ecosystem function, the latitudinal patterns of ecosystem multifunctionality (EMF) and how microbial communities affect EMF along a latitudinal gradient remain unclear. Here, we collected channel sediments, riparian rhizosphere soils, and riparian bulk soils from 30 rivers across China and calculated EMF using 18 variables related to nitrogen cycling, nutrient pool, plant productivity, and water quality. We also determined microbial diversity (taxonomic and functional) and microbial network complexity using metagenomic sequencing. The results showed that EMF significantly decreased with increasing latitude in riparian rhizosphere and bulk soils but not in channel sediments. Microbial taxonomic and functional richness (observed species) in channel sediments were significantly higher in the low-latitude group than in the high-latitude group. However, microbial co-occurrence networks were more complex in the high-latitude group compared with the low-latitude group. Abiotic factors, primarily geographic and climatic factors, contributed more to EMF than microbial diversity and network complexity parameters in which only betweenness centralization had a significant relationship with EMF. Together, this study provides insight into the latitudinal pattern of EMF in rivers and highlights the importance of large-scale factors in explaining such latitudinal patterns.IMPORTANCEEcosystem multifunctionality (EMF) is the capacity of an ecosystem to provide multiple functions simultaneously. Microorganisms, as dominant drivers of belowground processes, have a profound effect on ecosystem functions. Although studies have revealed the latitudinal patterns of microbial community structure and single ecosystem function, the latitudinal patterns of EMF and how microbial communities affect EMF along a latitudinal gradient remain unclear. We collected channel sediments, riparian rhizosphere soils, and riparian bulk soils from 30 rivers along a latitudinal gradient across China and calculated EMF using 18 variables related to nitrogen cycling, nutrient pool, plant productivity, and water quality. This study fills a critical knowledge gap regarding the latitudinal patterns and drivers of EMF in river ecosystems and gives new insights into how microbial diversity and network complexity affect EMF from a metagenomic perspective.