Browsing by Author "Muthuramalingam, Pandiyan"

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    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 Visweswara
    The 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.
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    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.