Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Manual correction of genome annotation improved alternative splicing identification of Artemisia annua.

Gene annotation is essential for genome-based studies. However, algorithm-based genome annotation is difficult to fully and correctly reveal genomic information, especially for species with complex genomes. Artemisia annua L. is the only commercial resource of artemisinin production though the content of artemisinin is still to be improved. Genome-based genetic modification and breeding are useful strategies to boost artemisinin content and therefore, ensure the supply of artemisinin and reduce costs, but better gene annotation is urgently needed. In this study, we manually corrected the newly released genome annotation of A. annua using second- and third-generation transcriptome data. We found that incorrect gene information may lead to differences in structural, functional, and expression levels compared to the original expectations. We also identified alternative splicing events and found that genome annotation information impacted identifying alternative splicing genes. We further demonstrated that genome annotation information and alternative splicing could affect gene expression estimation and gene function prediction. Finally, we provided a valuable version of A. annua genome annotation and demonstrated the importance of gene annotation in future research.

A novel polysaccharide from Lonicerae Japonicae Caulis: Characterization and effects on the function of fibroblast-like synoviocytes.

A novel polysaccharide (LJCP-2b) was isolated from Lonicerae Japonicae Caulis, and its structural features were identified by molecular weight distribution, infrared spectrum, monosaccharide composition, methylation analysis and NMR. LJCP-2b was a homogeneous heteropolysaccharide with a molecular weight of 7.0 kDa and composed of glucose, galacturonic acid, galactose, arabinose, rhamnose, xylose, mannose and glucuronic acid. Structural analysis revealed that LJCP-2b was mainly consisted of 1,3,6-ß-D-Galp, 1,4-α-D-Glcp, 1,4,6-α-D-Glcp, 1,4-ß-D-Galp, 1,2,4-α-L-Rhap and 1,4-α-D-GalpA. In vitro experiments showed that LJCP-2b could affect the function of TNF-α-induced rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), including weakening cell viability, increasing apoptosis rate, decreased migration number and adhesion capacity, and reduced the levels of IL-6 and IL-1ß. These results indicated that LJCP-2b exhibited the activity of inhibiting the hyperproliferation and inflammatory response of RA-FLS, which may be developed for prevention or treatment of RA.