Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach.

Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially - 7.5, - 7.9, - 8.2, - 8.4, and - 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow.

Population diversity of bacterial endophytes from jute (Corchorus olitorius) and evaluation of their potential role as bioinoculants.

Endophytes are bacterial or fungal organisms associated with plants in an obligate or facultative manner. In order to maintain a stable symbiosis, many of the endophytes produce compounds that promote plant growth and help them adapt better to the environment. This study was conducted to explore the potential of jute bacterial endophytes for their growth promotion ability in direct and indirect ways. A total of 27 different bacterial species were identified from different varieties of a jute plant (Corchorus olitorius) and different parts of the plant (leaf, root, seed, and seedling) based on 16S rRNA gene sequence. Two of the isolates showed ACC deaminase activity with Staphylococcus pasteuri strain MBL_B3 and Ralstonia solanacearum strain MBL_B6 producing 18.1 and 8.08 µM mg-1 h-1 α-ketobutyrate respectively while eighteen had the ACC deaminase gene (acdS). Fourteen were positive for siderophore activity while Kocuria sp. strain MBL_B19 (133.36 µg/ml) and Bacillus sp. strain MBL_B17 (124.72 µg/ml) showed high IAA production ability. Seven bacterial strains were able to fix nitrogen with only one testing positive for nifH gene. Five isolates exhibited phosphorus utilization ability with Bacillus sp. strain MBL_B17 producing 218.47 µg P/ml. Three bacteria were able to inhibit the growth of a phytopathogen, Macrophomina phaseolina and among them Bacillus subtilis strain MBL_B4 was found to be the most effective, having 82% and 53% of relative inhibition ratio (RIR) and percent growth inhibition (PGI) values respectively. Nine bacteria were tested for their in vivo growth promotion ability and most of these isolates increased seed germination potential and vigour index significantly. Bacillus subtilis strain MBL_B13 showed 26.8% more vigour index than the control in which no bacterial inoculum was used. All inoculants were found to increase the dry weight of jute seedlings in comparison to the control plants and the most increase in fresh weight was found for Staphylococcus saprophyticus strain MBL_B9. Staphylococcus pasteuri strain MBL_B3 exhibited diverse in vitro growth promotion activity and significant growth promoting effect in in vivo pot experiments. These bacterial strains with plant growth enhancing abilities have the potential to be used as bioinoculants.