School Of Basic And Applied Sciences
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Item In silico evaluation of natural compounds to confirm their anti-DNA gyrase activity(Springer, 2023-06-03T00:00:00) Kumar, Reetesh; Srivastava, Yogesh; Maji, Somnath; Siddiqui, Seemab; Tyagi, Rajeev Kumar; Muthuramalingam, Pandiyan; Singh, Sunil Kumar; Tiwari, Savitri; Verma, Geetika; de Toledo Thomazella, Daniela Paula; Shin, Hyunsuk; Prajapati, Dinesh Kumar; Rai, Pankaj Kumar; Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; de Moraes, Fabio Rogerio; Rao, Pasupuleti VisweswaraThe slow clearance of bacteria owing to drug resistance to the currently available antibiotics has been a global public health issue. The development of antibiotic resistance in Staphylococcus aureus has become prevalent in community-acquired infections, posing a significant challenge. DNA gyrase, an enzyme essential in all bacteria but absent in higher eukaryotes, emerges as an attractive target for novel antibacterial agents. This type II topoisomerase introduces negative supercoils in double-stranded DNA, at the expense of ATP, during DNA replication. In this study, we conducted a comprehensive screening of natural compound libraries from the ZINC database using different computational approaches targeting DNA gyrase activity. We identified five promising compounds following a detailed screening of drug-like compounds using pharmacokinetic-based studies, including the determination of the compound absorption, distribution, metabolism, excretion, and toxicity. Furthermore, based on protein�ligand docking studies, we showed the position, orientation, and binding affinity of the selected compounds within the active site of DNA gyrase. Overall, our study provides a primary reference to explore the molecular mechanisms associated with the antibacterial activity of the selected compounds, representing an important step toward the discovery of novel DNA gyrase inhibitors. Further investigation involving structural optimization as well as comprehensive in vivo and in vitro evaluations are necessary to fully explore the potential of these chemicals as effective antibacterial agents. Graphical abstract: [Figure not available: see fulltext.]. � 2023, The Author(s) under exclusive licence to Archana Sharma Foundation of Calcutta.Item Unveiling the mechanism of platelet dysfunction in Parkinson's disease: The effect of 6-hydroxydopamine on human blood platelets(Elsevier Ltd, 2023-05-22T00:00:00) Beura, Samir Kumar; Yadav, Pooja; Panigrahi, Abhishek Ramachandra; Singh, Sunil KumarIntroduction: Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure. Methods: To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H2DCF-DA (20 ?M), while mitochondrial ROS was evaluated using MitoSOX� Red (5 ?M), and intracellular Ca2+ was measured with Fluo-4-AM (5 ?M). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope. Results: Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca2+ elevation. This effect was mitigated by the Ca2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA. Conclusion: Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP3 receptor-Ca2+-NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients. � 2023 Elsevier LtdItem Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis(MDPI, 2023-03-28T00:00:00) Kumar, Reetesh; Srivastava, Yogesh; Muthuramalingam, Pandiyan; Singh, Sunil Kumar; Verma, Geetika; Tiwari, Savitri; Tandel, Nikunj; Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; Maji, Somnath; Sharma, Prakriti; Rai, Pankaj Kumar; Prajapati, Dinesh Kumar; Shin, Hyunsuk; Tyagi, Rajeev K.Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system�s evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection. � 2023 by the authors.Item Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release(Academic Press Inc., 2022-08-28T00:00:00) Yadav, Pooja; Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; Bhardwaj, Taniya; Giri, Rajanish; Singh, Sunil KumarPlatelet-derived microvesicles (PMVs) are the most abundant microvesicles in circulation, originating from blood platelets via membrane blebbing. PMVs act as biological cargo carrying key molecules from platelets, including immunomodulatory molecules, growth factors, clotting molecules, and miRNAs that can regulate recipient cellular functions. Formation and release of PMVs play an essential role in the pathophysiology of vascular diseases such as hemostasis, inflammation, and thrombosis. Platelet activation is considered the critical event in thrombosis, and a growing number of evidence suggests that oxidative stress-mediated signaling plays a significant role in platelet activation. Ca2+ is a notable player in the generation of ROS in platelets. Reports have established that microvesicles exhibit dual nature in redox mechanisms as they possess both pro-oxidant and antioxidant machinery. However, the impact of PMVs and their ROS machinery on platelets is still a limited explored area. Here, we have demonstrated that PMVs mediate platelet activation via intracellular ROS generation. PMVs interacted with platelets and induced calcium-mediated intracellular ROS production via NADPH oxidase (NOX), leading to platelet activation. Our findings will open up new insights into the tangible relationship of PMVs with platelets and will further contribute to the therapeutic aspects of PMVs in vascular injury and tissue remodeling. � 2022Item Role of platelet in Parkinson's disease: Insights into pathophysiology & theranostic solutions(Elsevier Ireland Ltd, 2022-07-04T00:00:00) Beura, Samir Kumar; Panigrahi, Abhishek Ramachandra; Yadav, Pooja; Singh, Sunil KumarParkinson's disease (PD) is the second-most-common neurodegenerative disease characterized by motor and non-motor dysfunctions, which currently affects about 10 million people worldwide. Gradual death and progressive loss of dopaminergic neurons in the pars compacta region of substantia nigra result in striatal dopamine deficiency in PD. Specific mutation with further aggregation of ??synuclein in the intraneuronal inclusion bodies is considered the neuropathological hallmark of this disease. PD is often associated with various organelle dysfunctions inside a dopaminergic neuron, including mitochondrial damage, proteasomal impairment, and production of reactive oxygen species, thus causing subsequent neuronal death. Apart from several genetic and non-genetic risk factors, emerging research establishes an association between cardiovascular diseases, including coronary heart disease, myocardial infarction, congestive heart failure, and ischemic stroke with PD. The majority of these cardiovascular diseases have an origin from atherosclerosis, where endothelial dysfunction following thrombus formation is significantly regulated by blood platelet. This non-nucleated cell fragment expresses not only neuron-specific molecules and receptors but also several PD-specific biomarkers such as ?-synuclein, parkin, PTEN-induced kinase-1, tyrosine hydroxylase, dopamine transporter, thus making platelet a suitable peripheral model for PD. Besides its similarity with a dopaminergic neuron, platelet structural alterations, as well as functional abnormalities, are also evident in PD. However, the molecular mechanism behind platelet dysfunction is still elusive and quite controversial. This state-of-the-art review describes the detailed mechanism of platelet impairment in PD, addressing the novel platelet-associated therapeutic drug candidates for plausible PD management. � 2022 Elsevier B.V.Item Does Water Play a Crucial Role in the Growth of ZnO Nanoclusters in ZnO/Cu Catalyst?(American Chemical Society, 2023-05-04T00:00:00) Dastider, Saptarshi Ghosh; Panigrahi, Abhishek Ramachandra; Banerjee, Arup; Haldar, Krishna Kanta; Fortunelli, Alessandro; Mondal, KrishnakantaThe catalytically active configuration of ZnO/Cu in the commercial ZnO/Cu/Al2O3 catalyst for methanol synthesis from CO2 is still not clear. In this study, we employ density functional theory based methods to shed light on the structure and stoichiometry of ZnO clusters both free in the gas phase and also deposited on the Cu(111) surface under methanol synthesis conditions. Specifically, we investigate the structural evolution of ZnO clusters in the presence of hydrogen and water. We find that the stability of ZnO clusters increases with the concentration of water until the ratio of Zn and OH in the clusters reaches 1:2, with a morphological transition from planar to 3D configurations for clusters containing more than 4 Zn atoms. These clusters exhibit weak interaction with CO2, and water is predicted to block the active center. The Cu(111) surface plays an important role in enhancing the adsorption of CO2 on the ZnO/Cu(111) systems. We infer that ZnO nanostructures covered with OH species may be the morphology of the ZnO during the methanol synthesis from the hydrogenation of CO2 on the industrial catalyst. � 2023 American Chemical Society.Item Dumbbell-Shaped Ternary Transition-Metal (Cu, Ni, Co) Phosphate Bundles: A Promising Catalyst for the Oxygen Evolution Reaction(American Chemical Society, 2022-01-27T00:00:00) Singh, Harjinder; Biswas, Rathindranath; Ahmed, Imtiaz; Thakur, Pooja; Kundu, Avinava; Panigrahi, Abhishek Ramachandra; Banerjee, Biplab; Halder, Krishna Kamal; Lahtinen, Jouko; Mondal, Krishnakanta; Haldar, Krishna KantaDevelopment of economical and high-performance electrocatalysts for the oxygen evolution reaction (OER) is of tremendous interest for future applications as sustainable energy materials. Here, a unique member of efficient OER electrocatalysts has been developed based upon structurally versatile dumbbell-shaped ternary transition-metal (Cu, Ni, Co) phosphates with a three-dimensional (3D) (Cu2(OH)(PO4)/Ni3(PO4)2�8H2O/Co3(PO4)2�8H2O) (CNCP) structure. This structure is prepared using a simple aqueous stepwise addition of metal ion source approach. Various structural investigations demonstrate highly crystalline nature of the composite structure. Apart from the unique structural aspect, it is important that the CNCP composite structure has proved to be an excellent electrocatalyst for OER performance in comparison with its binary or constituent phosphate under alkaline and neutral conditions. Notably, the CNCP electrocatalyst displays a much lower overpotential of 224 mV at a current density of 10 mA cm-2 and a lower Tafel slope of 53 mV dec-1 with high stability in alkaline medium. In addition, X-ray photoelectron spectroscopy analysis suggested that the activity and long-term durability for the OER of the ternary 3D metal phosphate are due to the presence of electrochemically dynamic constituents such as Ni and Co and their resulting synergistic effects, which was further supported by theoretical studies. Theoretical calculations also reveal that the incredible OER execution was ascribed to the electron redistribution set off in the presence of Ni and Cu and the most favorable interaction between the *OOH intermediate and the active sites of CNCP. This work may attract the attention of researchers to construct efficient 3D ternary metal phosphate catalysts for various applications in the field of electrochemistry. � 2022 American Chemical Society.