Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro.

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50=2.3µM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3(∗)43 (EC50=4.0µM), 3(∗)20 (EC50=8.2µM) and 5(∗)362 (EC50=38.9µM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds.

[Efficacy and safety of sulbactam/cefoperazone for hepato-biliary infections].

We studied efficacy and safety of sulbactam/cefoperazone (SBT/CPT) in the treatment of biliary tract infections in hospitalized patients at 26 hospitals from February 1993 to March 1995. Secondary to dropout, 273 out of 338 patients entered in the study were evaluated, 127 patients with cholecystitis, 132 patients with cholangitis, and 14 patients with liver abscesses. Of these, 93 patients (34.1% had malignancy as an underlying disease. SBT/CPZ had an efficacy of 79.9% (218 patients; excellent: 52, good: 166), with the efficacy in patients with cholecystitis, cholangitis and liver abscess at 89.0% (113 patients), 77.3% (102 patients and 21.4% (3 patients), respectively. A significant difference (p < 0.05) was observed in the efficacy rates of patients with (59 patients [63.4%]) and without malignancy (159 patients [88.3%]). A total of 84 strains were isolated from bile specimens of 53 patients, and the major isolates were Escherichia coli, Pseudomonas aeruginosa and Enterococcus spp. Two or more bacterial strains were isolated simultaneously in 20 patients. Mild or moderate side effect (allergic reaction including rash etc.) were noted in 4 patients (1.18%), and laboratory abnormalities (increased GOT, etc.) were in 16 patients (4.71%) out of the total 338 patients. This study clearly demonstrated that SBT/CPZ retains its excellent clinical efficacy and safety profile, throughout its use over the past decade.