Synthesis and anti-hepatitis C virus activity of novel ethyl 1H-indole-3-carboxylates in vitro.

A series of ethyl 1H-indole-3-carboxylates 9a(1)(-)(6) and 9b(1)(-)(2) were prepared and evaluated in Huh-7.5 cells. Most of the compounds exhibited anti-hepatitis C virus (HCV) activities at low concentration. The selectivity indices of inhibition on entry and replication of compounds 9a(2) (>10; >16.7) and 9b(1) (>6.25; >16.7) were higher than those of the other evaluated compounds, including the lead compound Arbidol (ARB, 6; 15). Moreover, the selective index of inhibition on entry of compound 9a(3) (>6.25) was higher than that of ARB (6). Of these three initial hits, compound 9a(2) was the most poten

Trimelopter cordifolium (Hyacinthaceae subfam. Ornithogaloideae), a new species from South Africa

The study of wild and cultivated material of Trimelopter from the Northern Cape province of South Africa revealed an undescribed species that shows a unique syndrome of morphological characters. We here describe Trimelopter cordifolium based on plants approaching T. psammophorum but differing in its small, cordate, psammophorous leaf, shorter inflorescence and pedicels, smaller flowers and bracts, and more prominently sculptured ovary. We provide a complete morphological description as well as data on ecology and distribution. We also report new data and illustrations of T. psammophorum, which complement its scarce description in the protologue.This work was partly supported by H2020 Research and Innovation Staff Exchange Programme of the European Commission, Project 645636: ‘Insect-plant relationships: insights into biodiversity and new applications’ (FlyHigh) and the complementary supporting funds UAUSTI19-08, UAUSTI22-05, ACIE18-03, ACIE21-01, ACIE22-01, VIGROB2021-166, and VIGROB2022-166 (University of Alicante, Spain)

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans-Packaged In Vitro To Generate Infectious Defective Particles▿ †

Naturally occurring hepatitis C virus (HCV) subgenomic RNAs have been found in several HCV patients. These subgenomic deletion mutants, mostly lacking the genes encoding envelope glycoproteins, were found in both liver and serum, where their relatively high abundance suggests that they are capable of autonomous replication and can be packaged and secreted in viral particles, presumably harboring the envelope proteins from wild type virus coinfecting the same cell. We recapitulated some of these natural subgenomic deletions in the context of the isolate JFH-1 and confirmed these hypotheses in vitro. In Huh-7.5 cells, these deletion-containing genomes show robust replication and can be efficiently trans-packaged and infect naïve Huh-7.5 cells when cotransfected with the full-length wild-type J6/JFH genome. The genome structure of these natural subgenomic deletion mutants was dissected, and the maintenance of both core and NS2 regions was proven to be significant for efficient replication and trans-packaging. To further explore the requirements needed to achieve trans-complementation, we provided different combinations of structural proteins in trans. Optimal trans-complementation was obtained when fragments of the polyprotein encompassing core to p7 or E1 to NS2 were expressed. Finally, we generated a stable helper cell line, constitutively expressing the structural proteins from core to p7, which efficiently supports trans-complementation of a subgenomic deletion encompassing amino acids 284 to 732. This cell line can produce and be infected by defective particles, thus representing a powerful tool to investigate the life cycle and relevance of natural HCV subgenomic deletion mutants in vivo

Cell Clones Selected from the Huh7 Human Hepatoma Cell Line Support Efficient Replication of a Subgenomic GB Virus B Replicon

Tamarins (Saguinus species) infected by GB virus B (GBV-B) have recently been proposed as an acceptable surrogate model for hepatitis C virus (HCV) infection. The availability of infectious genomic molecular clones of both viruses will permit chimeric constructs to be tested for viability in animals. Studies in cells with parental and chimeric constructs would also be very useful for both basic research and drug discovery. For this purpose, a convenient host cell type supporting replication of in vitro-transcribed GBV-B RNA should be identified. We constructed a GBV-B subgenomic selectable replicon based on the sequence of a genomic molecular clone proved to sustain infection in tamarins. The corresponding in vitro-transcribed RNA was used to transfect the Huh7 human hepatoma cell line, and intracellular replication of transfected RNA was shown to occur, even though in a small percentage of transfected cells, giving rise to antibiotic-resistant clones. Sequence analysis of GBV-B RNA from some of those clones showed no adaptive mutations with respect to the input sequence, whereas the host cells sustained higher GBV-B RNA replication than the original Huh7 cells. The enhancement of replication depending on host cell was shown to be a feature common to the majority of clones selected. The replication of GBV-B subgenomic RNA was susceptible to inhibition by known inhibitors of HCV to a level similar to that of HCV subgenomic RNA

Cell specific expression of genes coding for human plasmaproteins

International audienc

Heterocyclic compounds used in the treatment of kinetoplastid infection and their preparation

The invention relates to compds. of formula I, pharmaceutical compns. comprising these compds., their use in the treatment of kinetoplastid infections and their prepn. Compds. of formula I, wherein A is absent, O, S, etc.; B is absent, (CH2)​n and CO; Z is absent, CO, SO2, etc.; X and Y are independently H, halo, C1-​6 alkyl, etc.; m and n are 1 or 2 wherein at least one must be 1; p is 0 , 1 and 2; Het is 1H-​imidazole, 4H-​1,​2,​4-​triazole, oxazole, etc.; R1 is naphthalen-​2-​yl, 2-​methoxyquinolin-​3-​yl, pryimdin-​5-​yl, etc.; R2 is H, C6-​10 aryl, C3-​15 heterocyclyl, etc.; and pharmaceutically acceptable salts, tautomers and stereoisomers thereof, are claimed. Compd. II.bul.TFA was prepd. using a multistep procedure (procedure given)​. Compds. of the invention were tested for their inhibitory activity against T. brucei (data given)​