The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a long pandemic, with numerous cases and victims worldwide and enormous consequences on social and economic life. Although vaccinations have proceeded and provide a valuable shield against the virus, the approved drugs are limited and it is crucial that further ways to combat infection are developed, that can also act against potential mutations. The main protease (M pro ) of the virus is an appealing target for the development of inhibitors, due to its importance in the viral life cycle and its high conservation among different coronaviruses. Several compounds have shown inhibitory potential against M pro , both in silico and in vitro , with few of them also having entered clinical trials. These candidates include: known drugs that have been repurposed, molecules specifically designed based on the natural substrate of the protease or on structural moieties that have shown high binding affinity to the protease active site, as well as naturally derived compounds, either isolated or in plant extracts. The aim of this work is to collectively present the results of research regarding M pro inhibitors to date, focusing on the function of the compounds founded by in silico simulations and further explored by in vitro and in vivo assays. Creating an extended portfolio of promising compounds that may block viral replication by inhibiting M pro and by understanding involved structure-activity relationships, could provide a basis for the development of effective solutions against SARS-CoV-2 and future related outbreaks.

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To reveal the self-coordination mechanism of the fragile ecosystem of alpine tundra, we explored the relationship between soil microorganisms and other elements. On the alpine tundra of the Changbai Mountain, different vegetation types, altitudes and soil properties were selected as driving factors of soil microbial community. Soil microbial community, C- and N-cycling functional microbial and fungal biomass were analyzed. Structural equation model was used to study the control of biotic and abiotic factors in rhizosphere soil microbial community. The results showed that the pH value of soil had the strongest direct impact on the diversity and community structure of soil microorganisms, and had significant correlation with most of the C- and N-cycling functional microbial; organic carbon and vegetation also have strongest direct effect on fungal biomass, but all of them were not main factors influence soil microbial community structure, the elevation was the main controlling factor. In addition, the elevation mainly through indirect action affects the soil microbial community by driving distribution of plant species, soil organic carbon and pH value. This finding highlighted that elevation was the main predictor to determine rhizosphere microbial community structure but not vegetation in alpine tundra of Changbai Mountain.

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Elevational gradients are associated not only with variations in temperature and precipitation, but also with shifts in vegetation types and changes in soil physicochemical properties. While large-scale elevational patterns of soil microbial diversity, such as monotonic declines and hump-shaped models, have been reported, it is unclear whether within-ecosystem elevational distribution patterns exist for soil fungal communities at the small scale. Using Illumina Miseq DNA sequencing, we present a comprehensive analysis of soil fungal diversity and community compositions in an alpine tundra ecosystem at elevations ranging from 2000 to 2500 m on the Changbai Mountain, China. Soil fungal community composition differed among elevations, and the fungal diversity (i.e., species richness and Chao1) increased along elevations. Soil fungal richness was negatively correlated with soil carbon/nitrogen (C/N) ratio, and community composition varied according to the C/N ratio. In addition, the relative abundances of Basidiomycota and Leotiomycetes were similarly negatively correlated with C/N ratio. For functional guilds, our data showed that mycoparasite and foliar epiphyte abundances were also influenced by C/N ratio. These results indicated that soil C/N ratio might be a key factor in determining soil fungal distribution at small-scale elevational gradients.

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Spatio-temporal patterns of snowmelt and flowering times affect fruiting success in Erythronium grandiflorum Pursh (Liliaceae) in subalpine western Colorado, USA. From 1990 to 1995, I measured the consistency across years of snowmelt patterns and flowering times along a permanent transect. In most years since 1993, I have monitored fruit set in temporal cohorts (early- to late-flowering groups of plants) at one site. To assess 'pollination limitation', I have also conducted supplemental hand-pollination experiments at various times through the blooming season. The onset of blooming is determined by snowmelt, with the earliest years starting a month before the latest years owing to variation in winter snowpack accumulation. Fruit set is diminished or prevented entirely by killing frosts in some years, most frequently but not exclusively for the earlier cohorts. When frosts do not limit fruit set, pollination limitation is frequent, especially in the earlier cohorts. Pollination limitation is strongest for middle cohorts: it tends to be negated by frost in early cohorts and ameliorated by continuing emergence of bumble-bee queens in later cohorts. This lily appears to be poorly synchronized with its pollinators. Across the years of the study, pollination limitation appears to be increasing, perhaps because the synchronization is getting worse.

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In alpine ecosystems, microscale variation in snowmelt timing often causes different flowering phenology of the same plant species and seasonal changes in pollinator activity. We compared the variations in insect visitation, pollen dispersal, mating patterns, and sexual reproduction of Rhododendron aureum early and late in the flowering season using five microsatellites. Insects visiting the flowers were rare early in the flowering season (mid-June), when major pollinators were bumblebee queens and flies. In contrast, frequent visitations by bumblebee workers were observed late in the season (late July). Two-generation analysis of pollen pool structure demonstrated that quality of pollen-mediated gene flow was more diverse late in the season in parallel with the high pollinator activity. The effective number of pollen donors per fruit (N(ep)) increased late in the season (N(ep) = 2.2-2.7 early, 3.4-4.4 late). However, both the outcrossing rate (t(m)) and seed-set ratio per fruit were smaller late in the season (t(m) = 0.89 and 0.71, seed-set ratio = 0.52 and 0.18, early and late in the season, respectively). In addition, biparental inbreeding occurred only late in the season. We conclude that R. aureum shows contrasting patterns of pollen movement and seed production between early and late season: in early season, seed production can be high but genetically less diverse and, during late season, be reduced, possibly due to higher inbreeding and inbreeding depression, but have greater genetic diversity. Thus, more pollinator activity does not always mean more pollen movement.

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