Niranjan Behera

Computational Identification of Sweet Wormwood （Artemisia annua） microRNA and Their mRNA Targets

Despite its efficacy against malaria, the relatively low yield (0.01%-0.8%) of artemisinin in Artemisia annua is a serious limitation to the commercialization of the drug. A better understanding of the biosynthetic pathway of artemisinin and its regulation by both exogenous and endogenous factors is essential to improve artemisinin yield. Increasing evidence has shown that microRNAs (miRNAs) play multiple roles in various biological processes. In this study, we used previously known miRNAs from Arabidopsis and rice against expressed sequence tag (EST) database of A. annua to search for potential miRNAs and their targets in A. annua. A total of six potential miRNAs were predicted, which belong to the miR414 and miR1310 families. Furthermore, eight potential target genes were identified in this species. Among them, seven genes encode proteins that play important roles in artemisinin biosynthesis, including HMG-CoA reductase (HMGR), amorpha-4,11-diene synthase (ADS), farnesyl pyrophosphate synthase (FPS) and cytochrome P450. In addition, a gene coding for putative AINTEGUMENTA, which is involved in signal transduction and development, was also predicted as one of the targets. This is the first in silico study to indicate that miRNAs target genes encoding enzymes involved in artemisinin biosynthesis, which may help to understand the miRNA-mediated regulation of artemisinin biosynthesis in A. annua.

Molecular modeling and evaluation of binding mode and affinity of artemisinin-quinine hybrid and its congeners with Fe-protoporphyrin-IX as a putative receptor.

A recent rational approach to anti-malarial drug design is characterized as “covalent biotherapy” involves linking of two molecules with individual intrinsic activity into a single agent, thus packaging dual activity into a single hybrid molecule. In view of this background and reported anti malaria synergism between artemisinin and quinine; we describe the computer-assisted docking to predict molecular interaction and binding affinity of Artemisinin-Quinine hybrid and its derivatives with the intraparasitic haeme group of human haemoglobin. Starting from a crystallographic structure of Fe-protoporphyrin-IX, binding modes, orientation of peroxide bridge (Fe-O distance), docking score and interaction energy are predicted using the docking molecular mechanics based on generalized Born/surface area (MM-GBSA) solvation model. Seven new ligands were identified with a favourable glide score (XP score) and binding free energy (ΔG) with reference to the experimental structure from a data set of thirty four hybrid derivatives. The result shows the conformational property of the drug-receptor interaction and may lead to rational design and synthesis of improved potent artemisinin based hybrid antimalarial that target haemozoin formation.

Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards

Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn’t hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.

Diversity, population structure, and regeneration potential of tree species in five sacred forests of western Odisha, India

ABSTRACT From September 2015 to February 2016, we collected field data to study the tree species diversity, population structure and regeneration potential of five sacred forests of western Odisha, India, that differ in size, associated deities, and local communities. The close association of sacred forests with local people represents a community-based, participatory approach to conservation. Our quantitative analysis in five sites documented 78 tree species of 66 genera and 33 families. Tree density and species diversity were higher than previously reported for the forests of the Eastern Ghats, India. Population structure and regeneration potential in four out of five study sites showed a higher percentage of density in the seedling and sapling layers, demon-strating that these sites are regenerating. However, in the Gugarpat sacred forest, the population structure revealed large numbers of mature trees with a stable population structure. In our study, large proportions of species had either poor regeneration potential or were not regenerating. Hence, management strategies are needed to conserve these species. Our study documents the diversity, population patterns, and regeneration of the tree species of five sacred forests, which may help in further management and conservation of the biodiversity of sacred forests in India and globally.

Molecular modeling and prediction of binding mode and relative binding affinity of Art-Qui-OH with P. falciparum Histo-Aspartic Protease (HAP)

The relative binding affinity in terms of ΔΔG bind-cald value of the antimalarial compound artemisinin-quinine hybrid is primarily derived and is discussed in this article with reference to the ΔG bind-cald values of two known inhibitors Pepstatin-A and KNI-10006 complexed with HAP enzyme. The ΔG bind-cald value for KNI-10006 and Pepstatin-A is -14.10 kcal/mol and -13.09 kcal/mol respectively. The MM-GB/SA scoring results in the relative binding energy (ΔΔG bind-cald) of the hybrid molecule with respect to Pepstatin-A as 2.43 kcal/mol and 3.44 kcal/mol against KNI-10006. The overall binding mode of Art-Qui-OH resembles that of Pepstatin-A binding in HAP active site. We suggest here that the ΔΔG bind-cald value & proposed binding mode of the Art-Qui-OH for HAP enzyme should be considered for further structure-based drug design effort.