Molecular docking and dynamics studies for the identification of Nipah virus glycoprotein inhibitors from Indian medicinal plants.

The infection by Nipah Virus (NiV), a zoonotic paramyxovirus, is fatal and several outbreaks have been reported in humans in various countries. No effective vaccines or drugs are developed till date to control this infection. The NiV-Glycoprotein (NiV-G) is one of the essential proteins for viral entry by binding to the Ephrin-B receptors. The present study screens the potential phytocompounds that can target NiV-G and thereby inhibit the viral entry to human. Computer-aided virtual screening of 1426 phytocompounds from various medicinal plants was carried out to investigate their efficacy as potential therapeutics. Ribavirin, the currently used drug, was also docked to compare the docking score and intermolecular interactions between ligand and target protein. Further, molecular dynamics simulations and MM-PBSA binding free energy calculations were performed to understand the stability of the docked complexes. Radius of gyrations and Solvent Accessible Surface Area were also performed to evaluate the compactness and solvent behaviour of ligand-receptor complexes during the 100 ns simulation. Our analysis revealed that the alkaloid, Serpentinine, has the highest potency to block NiV-G with favourable binding.Communicated by Ramaswamy H. Sarma.

In silico screening of the phytochemicals present in Clitoria ternatea L. as the inhibitors of snake venom phospholipase A2 (PLA2).

Millions of people suffer from snake bite envenomation, and its management is a challenge, even today. Medicinal plants have attracted the researcher's attention for their outstanding advantages in treating many diseases, including snake venom poisoning. Clitoria ternatea L, is a plant popularly known for its various pharmacological effects especially, anti-snake venom property. However, the molecular mechanism behind this is poorly understood. It is reported that snake venom PLA2 is an extensively studied toxic factor. This study is meant to screen the compound's capability to act as inhibitors of the Daboia russelli snake venom PLA2 through molecular docking and dynamics studies. Our results show that among the 27 compounds taken for the study, only Kaempferol showed good interaction profile with the conserved catalytic active site residues, His48 and Asp49. The pharmacophore features of the compound also demonstrate its exact fitting at the binding pocket. Further RMSD, RMSF, Rg, and hydrogen bond analysis confirmed the stable binding of Kaempferol with PLA2 through molecular dynamic simulations for 100 ns. In addition, the MM/PBSA binding free energy calculation of the complex was also affirming the docking results. The binding free energy (BFE) of Kaempferolis better than the reference compound. ADME and Lipinski's rule of five reveals its drug like properties.Communicated by Ramaswamy H. Sarma.

Identification of potential lead compounds against BACE1 through in-silico screening of phytochemicals of Medhya rasayana plants for Alzheimer's disease management.

Alzheimer's disease is a progressive and irreversible neurodegenerative disease that accounts for 70-80% of dementia in the elderly. According to recent clinical data, the incidence of the disease is exponentially increasing with age. Beta-site amyloid precursor protein cleaving enzyme1 (BACE1) is an important molecule involved in the pathogenesis of Alzheimer's disease due to its early role in the amyloid cascade. Cleavage of amyloid precursor protein by BACE1 is the rate-limiting step leading to the production and aggregation of amyloid-beta plaques. A number of natural products are being identified as non-competitive BACE1 inhibitors. In Ayurveda, Medhya rasayana is a group of medicinal herbs, specifically used for managing neurological disorders and is known to be effective in improving cognitivity and intellect. This study aimed to analyze the pharmacological activity of bio-active compounds in Medhya rasayana plants against BACE1, employing structure-based docking approach. 11 compounds out of 876 were identified as potential hits, based on docking scores, binding energies, and interactions with the critical residues of BACE1. Possible neurological activities of these compounds were predicted using PASS server. Out of the 11 compounds screened, two compounds, 'Convolidine' from the plant Convolvulus pleuricaulis Choisy and 'N-(4-hydroxybutyl) phthalimide' from Glycyrrhiza glabra satisfied the pharmacological parameters of Lipinski rule of filtering and ADMET prediction. The binding stability of these compounds against BACE1 was confirmed by molecular dynamic simulation and post dynamic MM/GBSA calculations. Detailed analysis of the interaction with the critical amino acids in the active site revealed the possible inhibitory potential of these compounds of medicinal plant origin against BACE1.

Rutaretin1'-(6″-sinapoylglucoside): promising inhibitor of COVID 19 mpro catalytic dyad from the leaves of Pittosporum dasycaulon miq (Pittosporaceae).

SARS CoV2 is a novel strain of coronavirus, first reported in Wuhan of China, in 2019 and drugs specific to COVID-19 treatment are still lacking. The main protease (3CL) present in the new coronavirus strain is considered a potential drug target due to its role in viral replications. The plant Pittosporum dasycaulon Miq. is a medicinal plant reported to have prominent antimicrobial including antibacterial and antifungal activity. In this study, 12 natural compounds were selected on the basis of major peaks observed in the LC-HRMS analysis of P. dasycaulon aqueous leaves extract (AQLE). The pharmacological properties of the selected compounds against 3CLpro were investigated through in silico studies along with the standard antiviral drugs Lopinavir and Nelfinavir. The molecular docking study was done using Autodock 4.2 tool and visualized using Pymol (1.7.4.5 Edu). The docking analysis revealed that three compounds showed a better binding affinity than the standard drug Lopinavir. To validate the docking interactions, behaviour and stability of protein- ligand complex, molecular dynamics (100 ns) simulations were performed with the four best-ranked bioactive compounds identified through molecular docking analysis namely; Leptinidine, Rutaretin1'-(6″-sinapoylglucoside), Kalambroside A, and 5,7-dimethoxy', 4'methylenedioxyflavanone. The stability of the docking conformation was studied in depth by calculating the binding free energy using MM-PBSA method. Our findings on molecular docking, MD simulations and binding energy calculations suggest that Rutaretin1'-(6''-sinapoylglucoside) could be a potential inhibitor of COVID-19 3CLpro. However, considering the current pandemic situation of COVID-19, further research is required to experimentally validate their potential medicinal use against COVID-19 3CLpro both in vitro and in vivo along with clinical practices. Communicated by Ramaswamy H. Sarma.

Complete chloroplast genome of the medicinal plant Evolvulus alsinoides: comparative analysis, identification of mutational hotspots and evolutionary dynamics with species of Solanales.

Evolvulus alsinoides, belonging to the family Convolvulaceae, is an important medicinal plant widely used as a nootropic in the Indian traditional medicine system. In the genus Evolvulus, no research on the chloroplast genome has been published. Hence, the present study focuses on annotation, characterization, identification of mutational hotspots, and phylogenetic analysis in the complete chloroplast genome (cp) of E. alsinoides. Genome comparison and evolutionary dynamics were performed with the species of Solanales. The cp genome has 114 genes (80 protein-coding genes, 30 transfer RNA, and 4 ribosomal RNA genes) that were unique with total genome size of 157,015 bp. The cp genome possesses 69 RNA editing sites and 44 simple sequence repeats (SSRs). Predicted SSRs were randomly selected and validated experimentally. Six divergent hotspots such as trnQ-UUG, trnF-GAA, psaI, clpP, ndhF, and ycf1 were discovered from the cp genome. These microsatellites and divergent hot spot sequences of the Taxa 'Evolvulus' could be employed as molecular markers for species identification and genetic divergence investigations. The LSC area was found to be more conserved than the SSC and IR region in genome comparison. The IR contraction and expansion studies show that nine genes rpl2, rpl23, ycf1, ycf2, ycf1, ndhF, ndhA, matK, and psbK were present in the IR-LSC and IR-SSC boundaries of the cp genome. Fifty-four protein-coding genes in the cp genome were under negative selection pressure, indicating that they were well conserved and were undergoing purifying selection. The phylogenetic analysis reveals that E. alsinoides is closely related to the genus Cressa with some divergence from the genus Ipomoea. This is the first time the chloroplast genome of the genus Evolvulus has been published. The findings of the present study and chloroplast genome data could be a valuable resource for future studies in population genetics, genetic diversity, and evolutionary relationship of the family Convolvulaceae. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01051-w.

Green synthesis and characterization of zinc oxide nanoparticles using Cayratia pedata leaf extract.

The synthesis of Zinc oxide nanoparticles using a plant-mediated approach is presented in this paper. The nanoparticles were successfully synthesized using the Nitrate derivative of Zinc and plant extract of the indigenous medicinal plant Cayratia pedata. 0.1 mM of Zn (NO3)2.6H2O was made to react with the plant extract at different concentrations, and the reaction temperature was maintained at 55 °C, 65 °C, and 75 °C. The yellow coloured paste obtained was wholly dried, collected, and packed for further analysis. In the UV visible spectrometer (UV-Vis) absorption peak was observed at 320 nm, which is specific for Zinc oxide nanoparticles. The characterization carried out using Field Emission Scanning Electron Microscope (FESEM) reveals the presence of Zinc oxide nanoparticles in its agglomerated form. From the X-ray diffraction (XRD) pattern, the average size of the nanoparticles was estimated to be 52.24 nm. Energy Dispersive Spectrum (EDX) results show the composition of Zinc and Oxygen, giving strong energy signals of 78.32% and 12.78% for Zinc and Oxygen, respectively. Fourier Transform - Infra-Red (FT-IR) spectroscopic analysis shows absorption peak of Zn-O bonding between 400 and 600 cm-1. The various characterization methods carried out confirm the formation of nano Zinc oxide. The synthesized nanoparticles were used in the immobilization of the enzyme Glucose oxidase. Relative activity of 60% was obtained when Glucose oxidase was immobilized with the green synthesized ZnO nanoparticles. A comparative study of the green synthesized with native ZnO was also carried out. This green method of synthesis was found to be cost-effective and eco-friendly.

High Quality Draft Genome of Arogyapacha (Trichopus zeylanicus), an Important Medicinal Plant Endemic to Western Ghats of India.

Arogyapacha, the local name of Trichopus zeylanicus, is a rare, indigenous medicinal plant of India. This plant is famous for its traditional use as an instant energy stimulant. So far, no genomic resource is available for this important plant and hence its metabolic pathways are poorly understood. Here, we report on a high-quality draft assembly of approximately 713.4 Mb genome of T. zeylanicus, first draft genome from the genus Trichopus The assembly was generated in a hybrid approach using Illumina short-reads and Pacbio longer-reads. The total assembly comprised of 22601 scaffolds with an N50 value of 433.3 Kb. We predicted 34452 protein coding genes in T. zeylanicus genome and found that a significant portion of these predicted genes were associated with various secondary metabolite biosynthetic pathways. Comparative genome analysis revealed extensive gene collinearity between T. zeylanicus and its closely related plant species. The present genome and annotation data provide an essential resource to speed-up the research on secondary metabolism, breeding and molecular evolution of T. zeylanicus.

The Complete Chloroplast Genome of Trichopus zeylanicus, And Phylogenetic Analysis with Dioscoreales.

CORE IDEAS: We presents the first chloroplast genome from the genus Trichopus. Comparative analysis revealed that the IR regions are more conserved than the SC regions. Highly divergent sequence hot spots were identified, which could be used as molecular markers. Phylogenetic analysis gave insight into the evolutionary history of Trichopus zeylanicus. In this study, we determined the complete sequence of the chloroplast genome of an important, rare, and endangered medicinal plant, Trichopus zeylanicus. The analysis of the genome showed that the complete chloroplast genome of Trichopus zeylanicus is 153,497 bp in size, and has a quadripartite structure with a large single copy of 81,091 bp and a small single copy of 17,512 bp separated by inverted repeats of 27,447 bp. Sequence analysis revealed that the chloroplast genome encodes 112 unique genes, including 78 protein-coding genes, 30 tRNA genes, and four rRNA genes. We also identified 95 simple sequence repeats and 54 long repeats including 34 forward repeats, seven inverted repeats, nine palindromes, three reverse repeats, and one complementary repeat within the chloroplast genome of Trichopus zeylanicus. Whole chloroplast genome comparison with those of other Dioscoreales indicated that the inverted regions are more conserved than large single copy and small single copy regions. In the phylogenetic trees based on complete chloroplast genome and 78 shared chloroplast protein-coding genes in 15 monocot species, including 14 Dioscoreales, Trichopus zeylanicus formed a distinct clade. In summary, the first chloroplast genome from the genus Trichopus reported in this study gave a better insight into the phylogenetic relationships of different genera within the order Dioscoreales. Moreover, the present data will be a valuable chloroplast genomic resource for population genetics.

Studies on neutralizing effect of Ophiorrhiza mungos root extract against Daboia russelii venom.

ETHNOPHARMACOLOGICAL RELEVANCE: The folklore or traditional therapy in southern India widely utilizes a plethora of local herbs to treat the patients challenged with snake venom. Despite the widespread implementation of antisera therapy, the local population of the country still relies on this century's old medicinal formulas mainly due to the cost effectiveness, lesser side effects and also its cultural acceptability. The present study aims to validate the neutralizing ability of one such traditionally acclaimed antidote Ophiorrhiza mungos root extract against Russell's viper (Daboia russelii) venom in the early developing chick embryos. MATERIALS AND METHODS: The disc impregnated with venom, root extract or the combination of both was placed on the yolk sac membrane preferably over the anterior blood vessel of 6th day chick embryo. The neutralization/inhibition of venom-induced lethality or hemorrhage was achieved by incubating venom and extract before being applied to the embryo. The membrane stabilizing properties of root extract was estimated by HRBC lysis method. The preliminary phytochemical analysis was done to assess the phyto constituents in the root extract. RESULTS: The LD50 of Russell's viper venom in 6th day chick embryo was found to be 3 µg/µl. The neutralising effect of root extract was achieved by pre-incubating venom with various concentrations of extract and at the concentration of 10 µg/µl, 100% recovery of embryos was observed after 6h of incubation. Higher concentration of root extract showed remarkable results by completely abolishing traces of hemorrhagic lesions induced by viper venom. CONCLUSIONS: The above observations confirmed that the root extract of Ophiorrhiza mungos possess potent anti snake venom neutralizing compounds, which inhibit the activity of viper venom. The chick embryo, a new insensate model used in the present study is significant in venom research as it reduces the ruthless suffering of higher mammalian experimental models.