Flaviviruses, including dengue, West Nile and recently emerged Zika virus, are important human pathogens, but there are no drugs to prevent or treat these viral infections. The highly conserved Flavivirus NS2B-NS3 protease is essential for viral replication and therefore a drug target. Compound screening followed by medicinal chemistry yielded a series of drug-like, broadly active inhibitors of Flavivirus proteases with IC 50 as low as 120 nM. The inhibitor exhibited significant antiviral activities in cells (EC 68 : 300-600 nM) and in a mouse model of Zika virus infection. Xray studies reveal that the inhibitors bind to an allosteric, mostly hydrophobic pocket of dengue NS3 and hold the protease in an open, catalytically inactive conformation. The inhibitors and their binding structures would be useful for rational drug development targeting Zika, dengue and other Flaviviruses.
eThe anaerobic oxidation of ammonium (anammox) process has been observed in diverse terrestrial ecosystems, while the contribution of anammox to N 2 production in paddy soils is not well documented. In this study, the anammox activity and the abundance and diversity of anammox bacteria were investigated to assess the anammox potential of 12 typical paddy soils collected in southern China. Anammox bacteria related to "Candidatus Brocadia" and "Candidatus Kuenenia" and two novel unidentified clusters were detected, with "Candidatus Brocadia" comprising 50% of the anammox population. The prevalence of the anammox was confirmed by the quantitative PCR results based on hydrazine synthase (hzsB) genes, which showed that the abundance ranged from 1.16 ؋ 10 4 to 9.65 ؋ 10 4 copies per gram of dry weight. The anammox rates measured by the isotope-pairing technique ranged from 0.27 to 5.25 nmol N per gram of soil per hour in these paddy soils, which contributed 0.6 to 15% to soil N 2 production. It is estimated that a total loss of 2.50 ؋ 10 6 Mg N per year is linked to anammox in the paddy fields in southern China, which implied that ca. 10% of the applied ammonia fertilizers is lost via the anammox process. Anammox activity was significantly correlated with the abundance of hzsB genes, soil nitrate concentration, and C/N ratio. Additionally, ammonia concentration and pH were found to be significantly correlated with the anammox bacterial structure.
Although the geographical distribution patterns of microbes have been studied for years, few studies have focused on urban soils. Urbanization may have detrimental effects on the soil ecosystem through pollution discharge and changes in urban climate. It is unclear whether urbanization-related factors have any effect on soil bacterial communities. Therefore we investigated geographical patterns of soil microbial communities in parks in 16 representative Chinese cities. The microbial communities in these 95 soil samples were revealed by 454-pyrosequencing. There were 574,442 effective sequences among the total of 980,019 16S rRNA gene sequences generated, showing the diversity of the microbial communities. Proteobacteria, Actinobacteria, Acidobacteria, Planctomycetes, Chloroflexi and Bacteroidetes were found to be the six dominant phyla in all samples. Canonical correspondence analysis showed that pH, followed by annual average precipitation, annual average temperature, annual average relative humidity and city sunshine hours, Mn and Mg were the factors most highly correlated with the bacterial community variance. Urbanization did have an effect on bacterial community composition of urban park soils but it contributed less to the total variance compared with geographical locations and soil properties, which explained 6.19% and 16.78% of the variance, respectively.
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