A molecular epidemiological study of pediatric norovirus gastroenteritis, 2017-2019. / 2017~2019å¹´å„¿ç«¥è¯ºå¦‚ç— æ¯’ç›¸å ³æ€§èƒƒè‚ ç‚Žçš„åˆ†å­æµè¡Œç— å­¦ç ”ç©¶.

OBJECTIVES: To study the molecular epidemiological characteristics of norovirus in children with acute gastroenteritis from 2017 to 2019. METHODS: A retrospective analysis was performed on the medical data of children with acute gastroenteritis who were admitted to Children's Hospital of Chongqing Medical University from January 2017 to December 2019. A total of 1 458 stool samples were collected from the children, and viral RNA was extracted. Reverse transcription polymerase chain reaction was used for gene amplification, sequencing, and genotype identification of the VP1 region of capsid protein in norovirus. RESULTS: Among the 1 458 stool samples, 158 (10.8%) were positive for norovirus. There was no significant difference in the positive detection rate of norovirus between different years (P>0.05). Boys had a norovirus detection rate of 12.2% (105/860), which was significantly higher than that in girls (8.9%, 53/598) (P=0.043). The children aged 12 to <18 months had the highest norovirus detection rate (16.9%, 51/301). August, September, and October were the epidemic peak season. A total of 23 norovirus-positive samples were also positive for rotavirus. The norovirus detected were mainly GII type (97.5%, 154/158), and only 4 cases were GI type (2.5%, 4/158). The sequencing of the VP1 region of capsid protein in the positive samples showed that GII.4 (69.6%, 110/158) was the dominant genotype, among which 99 (62.7%, 99/158) were GII.4 Sydney 2012, followed by GII.3 (15.2%, 24/158), GII.2 (10.1%, 16/158), GII.6 (1.9%, 3/158), and GII.17 (0.6%, 1/158). GI.3 (1.3%, 2/158), GI.2 (0.6%, 1/158), and GI.5 (0.6%, 1/158) were rarely detected. CONCLUSIONS: Norovirus GII.4 Sydney 2012 was the major epidemic strain in the children with norovirus gastroenteritis from 2017 to 2019. Although norovirus infection can exist throughout the year, August to October is the peak period. During this period, norovirus surveillance and key population protection are strengthened to help prevent and control norovirus diarrhea.

Structure based virtual screening of novel noncompetitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype ionotropic glutamate receptors are attractive antiepileptic targets responsible for mediating the majority of excitatory neurotransmission and plasticity. The noncompetitive antagonists obtain more and more attention as drug candidates for treatment of the neurological diseases involving excessive activity of AMPARs, due to they regulate AMPA receptors (AMPARs) activity independently of endogenous glutamate levels unlike the competitive antagonists. Development of novel AMPAR noncompetitive antagonists, which are safer and more efficacious than competitive antagonists, is highly under demand. Here, we present the discovery of novel antagonists against AMPAR through Structure-Based Virtual Screening (SBVS). Three compounds were successfully distinguished by several different filtering strategies, namely STOCK6S-10902, STOCK1N-49134 and STOCK5S-68665. The interaction mode of these compounds was further explored through molecular dynamics simulation, binding free energy calculation and the binding free energy decomposition. It is demonstrated that some residues within the binding pocket, which have been proved their importance in antagonist binding and gating, form strong hydrogen bond interactions with these three molecules. In particular, H-bond interactions with high occupancies between Ser516, Ser788 and STOCK6S-10902 and Ser516, Asn791 and STOCK1N-49134 were observed. The three hit compounds with new scaffolds and the detailed binding modes could potentially serve as a starting point for further optimization and development.

pH effects on the structural dynamics of cutinase from Trichoderma reesei: insights from molecular dynamics simulations.

Cutinases are utilized in a variety of industries for the hydrolysis of a broad range of substrates, such as cutin, polyesters, soluble esters, insoluble short- and long-chain triglycerides. The novel cutinase from Trichoderma reesei (Tr) attracted much attention due to its two rare characteristics distinct from the classical cutinases: it possesses a lid covering its active site and its optimal activity at acidic pH. However, the structural basis for pH preference and the function of lid is still not well understood. In this work, total of six initial systems were set up either under acidic or basic pH conditions (closed-apo, open-apo and open-holo). Then, molecular dynamics (MD) simulations were performed to make a better understanding of structural dynamics of Tr cutinase under different pH conditions for the first time. The results mainly suggest that it is easier to open for the lid under an acidic pH condition. In addition, the binding of long-chain triglyceride is more stable at lower pH than higher pH. These findings elucidate that how pH influences Tr cutinase at the atomistic level. The structural and dynamic details would be useful for rational enzyme design for acidic cutinase.