Screening of HDAC3/8 Small Molecule Inhibitors from Traditional Chinese Medicine Based on Molecular Docking / 中国实验方剂学杂志

Objective::To discover a small molecule active ingredient of traditional Chinese medicine (TCM) with the inhibitory activity of histone deacetylase (HDAC) 3/8. Method::The molecular docking technique was performed by AutoDock 4.2.6 software. Trichostatin A (TSA) was used as a reference to screen 19 small molecular components from TCM, and the default docking conformation number was set to obtain the docking binding energy, active site amino acid residues and hydrogen bonds, and the biological activity was verified. Result::The binding energies of 19 small molecule components from TCM to HDAC3 and HDAC8 were different. Among them, ursolic acid, fangchinoline and tetrandrine have low binding energies to HDAC3 and HDAC8, and their binding activities were strong. The optimal binding energy of fangchinoline and HDAC3 at the site 1 was the lowest (-26.71 kJ·mol-1), and that of HDAC8 at the site 9 was the lowest (-26.84 kJ·mol-1). The optimal binding energy of tetrandrine and HDAC3 at the site 13 was the lowest (-26.38 kJ·mol-1), and that of HDAC8 at the site 12 was the lowest (-25.41 kJ·mol-1). In addition, the binding energy of ursolic acid and HDAC3 at the site 16 was the lowest (-25.83 kJ·mol-1), and that of HDAC8 at the site 8 was the lowest (-35.62 kJ·mol-1). Three kinds of amino acids at the docking site of small molecules were rendered by PyMOL 2.3.1.When ursolic acid was combined with HDAC3/8, the active sites produced two hydrogen bonds, and the interaction was strong, and many amino acids were connected at the active site. The fangchinoline formed two hydrogen bonds with the active site of HDAC3 and one hydrogen bond with the active site of HDAC8, and hydrophobic binding with some active site amino acids. There was no hydrogen bond between tetrandrine and HDAC3/8, and all docking sites were docked by 4 active amino acids. Three small molecules (ursolic acid, fangchinoline and tetrandrine) with the best docking effect had the inhibitory activity against HDAC3/8 at the concentration of 500 μmol·L-1 and 100 μmol·L-1, and the inhibitory activity was still optimal among the 10 selected small molecules. Conclusion::Among the screened 19 small molecules, ursolic acid, tetrandrine and fangchinoline may be the new anti-inflammatory drugs of HDAC3/8 inhibitory target, which provides a reference for further exploration and discovery of new anti-inflammatory drugs.

Psychomotor retardation with neutropenia for more than one year in a toddler / 中国当代儿科杂志

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.

Sequence analysis of the phosphoprotein gene of peste des petits ruminants virus of Chinese origin / 病毒学报

The nucleotide sequences of P gene from a field strain of peste des petits ruminants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The P gene is 1,655 nucleotides long with two overlapping open reading frames (ORFs). The first ORF is 1530 nucleotides long and would produce P protein of 509 amino acid residues. The second ORF is 534 nucleotides long and would produce C protein of 177 amino acid residues. The first ORF produces a second mRNA transcript of 897 nucleotides long with an extra G nucleotide at position 751. Translation from this mRNA would produce V protein of 298 amino acid residues. The nucleotide and deduced amino acid sequence were compared with the homologous region of other PPRV isolates. At the amino acid level, the "China/Tib/Gej/07-30" shares homology of 86.10%-97.3%, 84.3%-94.9%, and 82.9%-96.3% for P, C, and V proteins respectively. Several sequence motifs in the P genes were identified on the basis of conservation in the PPRVs and the morbilliviruses.

Sequence analysis of the matrix protein and fusion protein genes of a field peste des petits ruminants virus strain from Tibet, China / 病毒学报

The nucleotide sequences of M and F genes from a field strain of peste des petits ruminants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The M gene was 1 483 nucleotides in length with a single open reading frame (ORF), encoding a protein of 335 amino acids. The F gene was 2411 nucleotides in length, encoding a protein of 546 amino acids. The resulting nucleotide sequence and the deduced amino acid sequences were compared with the homologous regions of other PPRV isolates. The nucleotide sequences of M and F genes of the "China/Tib/Gej/07-30" was 92.4%-97.7% and 85.5%-96.1% identical to other PPRV isolates, respectively, while a homology of 97.0%-98.2% and 94.3%-98.2% could be observed at the amino acids level respectively. Several sequence motifs in the M and F genes had been identified on the basis of conservation in the PPRVs and the morbilliviruses. The 3' untranslated region of M gene was 443 nucleotides in length with 82.4%-93.5% identical to other PPRV isolates. The 5' untranslated region of F gene was 634 nucleotides in length with 76.2%-91.7% identical to other PPRV isolates.

Sequence analysis of the nucleocapsid gene and genome promoter region of peste des petits ruminants virus of Chinese origin / 病毒学报

The N gene and genome promoter nucleotide sequence of a Chinese Peste des petits rumiants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The length of N gene was 1689 nucleotides with a single open reading frame (ORF). The nucleotide and deduced amino acid sequence was compared with the homologous region of other PPRV isolates. The nucleotide sequence of the "China/Tib/Gej/07-30" was 91.7%-97.6% identical to other PPRV isolates, while a homology of 94.9%-98.5% could be observed at the amino acids level. The N gene encoded a protein of 525 amino acids. Several sequence motifs were identified on the basis of conservation in the PPRVs and the morbilliviruses. The genome length of promoter region was 107 nucleotides with 91.8%-98.2% identity to other PPRV isolates. Phylogenetic analysis showed that the "China/Tib/Gej/07-30" belonged to the Asian lineage.