Browsing by Author "Somesh Kumar"

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Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective
(Taylor and Francis Ltd., 2023) Somesh Kumar; Neha Choudhary; Mohammed Faruq; Arun Kumar; Ravindra K. Saran; Prem Kumar Indercanti; Vikram Singh; Haseena Sait; Sunita Jaitley; Martin Valis; Kamil Kuca; Sunil K. Polipalli; Manoj Kumar; Tejveer Singh; Prashanth Suravajhala; Rohit Sharma; Seema Kapoor
The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole–CypD complex is more stable than cyclosporin A (CsA)–CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings. Communicated by Ramaswamy H. Sarma. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Inferring Recombination Events in SARS-CoV-2 Variants In Silico
(Springer, 2023) Nihal Najeeb; Aparna B. Murukan; Anagha Renjitha; Malavika Jayaram; Ayisha A. Jabbar; Haripriya Haridasan; Akshara Prijikumar; Sneha Baiju; Adrial Ann Nixon; Ponnambil Anantha Krishnan; Sunu Rodriguez; Somesh Kumar; Sunil K. Polipalli; Keshav K. Singh; Bipin G. Nair; Sudeep D. Ghate; R. Shyama Prasad Rao; Polavarapu Bilhan Kavi Kishor; Arya Aloor; Renuka Suravajhala; Gyaneshwer Chaubey; Prashanth Suravajhala
Over the last 34 months, at least 10 severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) distinct variants have evolved. Among these, some were more infectious while others were not. These variants may serve as candidates for identification of the signature sequences linked to infectivity and viral transgressions. Based on our previous hijacking and transgression hypothesis, we aimed to investigate whether SARS-CoV-2 sequences associated with infectivity and trespassing of long noncoding RNAs (lncRNAs) provide a possible recombination mechanism to drive the formation of new variants. This work involved a sequence and structure-based approach to screen SARS-CoV-2 variants in silico, taking into account effects of glycosylation and links to known lncRNAs. Taken together, the findings suggest that transgressions involving lncRNAs may be linked with changes in SARS-CoV-2–host interactions driven by glycosylation events. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.