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Shiv Nadar University

(SoNS) School of Natural Sciences

We examine the possibility of artificial Hawking radiation by proposing a non-PT-symmetric weakly pseudo-Hermitian two-band model containing a tilting parameter by pursuing Weyl semimetal blackhole analogy. We determine the tunneling probability using such a Hamiltonian through the event horizon that acts as a classically forbidden barrier. © 2022 Author(s).

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Physics

Journal of Mathematical Physics

Artificial Hawking radiation, weak pseudo-Hermiticity, and Weyl semimetal blackhole analogy

Herein we report a hitherto novel multicomponent reaction involving pyridine and its derivatives, aryl diazoesters and N-alkylmaleimides (2 equivalents), using a blue LED under neat (solvent-free) conditions and in the absence of any metal catalysts or bases at r. t. to generate densely substituted itaconimides. This environmentally sustainable strategy generated the desired products in excellent yields. The reaction involved the carbene formation of aryl diazoesters from a blue LED and a subsequent generation of pyridine ylides. The pyridine ylides underwent [3 + 2] cycloaddition with N-alkyl maleimides followed by oxidation, subsequent ring opening of the [3 + 2] adducts and finally reaction with another molecule of N-alkyl maleimides to afford the desired itaconimide derivatives. The reaction has wide functional group tolerance at the aryl moiety of the diazoesters and also on pyridine. Control experiments and DFT studies were used to elucidate the reaction mechanism. © 2022 The Royal Society of Chemistry.

Chemistry

Green Chemistry

Blue LED induced solvent-free multicomponent reactions among aryl diazoacetates, pyridine derivatives and maleimides: direct eco-friendly synthesis of densely functionalized itaconimides

Both mechanically and electrically rechargeable zinc-air batteries (ZABs) have received much interest due to their high energy density and suitability for mobile and stationary applications. However, their commercialization has been impeded by the lack of robust, low-cost and environmentally benign catalyst materials that can be easily scaled up. In this context, the present work introduces a new type of transition metal-free catalytic material (AlOOH/NGr) by anchoring the pseudo-boehmite phase of aluminium oxyhydroxide (AlOOH) nanosheets over nitrogen-doped graphene (NGr) via a single-step and straightforward hydrothermal process. Furthermore, density functional theory (DFT) based computation demonstrates that the nucleation of AlOOH starts from the N-sites and points towards the strong surface interaction between AlOOH and NGr via doped nitrogen. AlOOH/NGr consisting of thin layered pseudo-boehmite sheets uniformly distributed over NGr has displayed an oxygen reduction reaction onset potential of 0.83 V and a half-wave potential of 0.72 V, along with good catalytic durability in alkaline medium. With this, AlOOH/NGr, when used as an air electrode for fabricating a primary Zn-air battery, the system has exhibited an open circuit voltage of ∼1.27 V with a flat discharge profile at a current rate of 10 mA cm−2. The fabricated system delivered a specific capacity of ∼720 mA h g−1 and a high power density of 204 mW cm−2 and is comparable to the counterpart system based on the state-of-the-art Pt/C (20 wt% Pt) cathode. Additionally, the homemade battery was able to maintain its performance after 4 times of mechanical recharging of the battery, which lasted for more than 35 h at a discharge current density of 10 mA cm−2. Thus, we have uncovered the potential of an earth-abundant metal-based catalytic system for fabricating and demonstrating a robust mechanically rechargeable zinc-air battery. © 2022 The Royal Society of Chemistry

Journal of Materials Chemistry A

A pseudo-boehmite AlOOH supported NGr composite-based air electrode for mechanically rechargeable Zn-air battery applications

Hepatitis E Virus (HEV) is a quasi-enveloped virus having a single-stranded, positive-sense RNA genome (~7.2 kb), flanked with a 5′ methylated cap and a 3′ polyadenylated tail. The HEV open reading frame 1 (ORF1) encodes a 186-kDa polyprotein speculated to get processed and produce Methyltransferase (MTase), one of the four essential replication enzymes. In this study, we report the identification of the MTase inhibitor, which may potentially deplete its enzymatic activity, thus causing the cessation of viral replication. Using in silico screening through docking, we identified ten putative compounds, which were tested for their anti-MTase activity. This resulted in the identification of 3-(4-Hydroxyphenyl)propionic acid (HPPA), with an IC50 value of 0.932 ± 0.15 μM, which could be perceived as an effective HEV inhibitor. Furthermore, the compound was tested for inhibition of HEV replication in the HEV culture system. The viral RNA copies were markedly decreased from ~3.2 × 106 in untreated cells to ~4.3 × 102.8 copies in 800 μM HPPA treated cells. Therefore, we propose HPPA as a potential drug-like inhibitor against HEV-MTase, which would need further validation through in vivo analysis using animal models and the administration of Pharmacokinetic and Pharmacodynamic (PK/PD) studies. © 2022 by the authors.

Life Sciences

Fulltext

Viruses

Inhibition of Hepatitis E Virus Replication by Novel Inhibitor Targeting Methyltransferase

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID. Copyright © 2022 Kulandaisamy, Kushwaha, Dalal, Kumar, Singh, Baswal, Sharma, Praneeth, Jorwal, Kayampeta, Sharma, Maddur, Kumar, Kumar, Polamarasetty, Singh, Sehgal, Gholap, Appaiahgari, Katika and Inampudi.

Frontiers in Microbiology

Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and in vitro Studies

Here we are presenting an automated computational pipeline used to mine 5976 mitochondrial genomes to identify common, polymorphic, and unique microsatellites also known as simple sequence repeats (SSRs). Microsatellites are repetitive motifs of 1–6 bases in a DNA sequence. Due to their abundance and highly polymorphic nature, microsatellites have become one of the widely used molecular/genetic markers valuable for many studies including gene tagging, genetic diversity, and species identification. Several computational tools dedicated to mine and categorize microsatellites in nucleotide sequences were developed; however, there is no tool which can identify unique, common and polymorphic microsatellites between each pair of nucleotide sequences. To explore such microsatellites, we have developed a fully automated computational pipeline named AutomAted RepeaT Identifier (AARTI). The AARTI is the only tool till date, which identifies common, polymorphic, and unique microsatellites between each pair of nucleotide sequences. The computational pipeline was constructed using the PERL programming language and the web server for the pipeline was developed with the help of PHP, HTML, CSS, and JavaScript. It was successfully tested to reproduce the results of previous study on 7 mitochondrial genomes of genus Orthotrichum. Moreover, the pipeline was also applied on 5846 (Metazoa) and 130 (Viridiplantae) mitochondrial genomes. The AARTI is freely available at https://lms.snu.edu.in/aarti/ and will certainly accelerate the studies of length variation in microsatellites between species. Additionally, it will be useful in comparative genomic studies, for the computational characterization of microsatellites, and has the potential to be a routine genome analysis pipeline for mitochondrial genomes. © 2022 Elsevier B.V. and Mitochondria Research Society

Mitochondrion

AutomAted RepeaT Identifier (AARTI): A tool to identify common, polymorphic, and unique microsatellites

Main conclusion: The integrated transcriptome data analyses suggested the plausible roles of lncRNAs during seed development in chickpea. The candidate lncRNAs associated with QTLs and those involved in miRNA-mediated seed size/weight determination in chickpea have been identified. Abstract: Long non-coding RNAs (lncRNAs) are important regulators of various biological processes. Here, we identified lncRNAs at seven successive stages of seed development in small-seeded and large-seeded chickpea cultivars. In total, 4751 lncRNAs implicated in diverse biological processes were identified. Most of lncRNAs were conserved between the two cultivars, whereas only a few of them were conserved in other plants, suggesting their species-specificity. A large number of lncRNAs differentially expressed between the two chickpea cultivars associated with seed development-related processes were identified. The lncRNAs acting as precursors of miRNAs and those mimicking target protein-coding genes of miRNAs involved in seed size/weight determination, including HAIKU1, BIG SEEDS1, and SHB1, were also revealed. Further, lncRNAs located within seed size/weight associated quantitative trait loci were also detected. Overall, we present a comprehensive resource and identified candidate lncRNAs that may play important roles during seed development and seed size/weight determination in chickpea. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Planta

Genome-wide analysis suggests the potential role of lncRNAs during seed development and seed size/weight determination in chickpea

We asked if transfer RNA (tRNA) ever got an opportunity of translating its own sequence during evolution, what would have been the function of such tRNA-encoded peptides (tREPs)? If not, could one artificially synthesize tREPs to study the corresponding functional outcomes? Here, we report a novel, first-in-the-class, chemically synthesized tREP-18 molecule originating from the Escherichia coli tRNA sequence showing potent antileishmanial property. As a first step, E. coli tRNAs were computationally translated into peptide sequence equivalents and a database of full-length hypothetical tREPs was created. The tREP sequences were sent into sequence, structure, and energy filters to narrow down potential peptides for experimental validation. Based on the functional predictions, tREPs were screened against antiparasitic targets, leading to the identification of tREP-18 as a potential antiparasitic peptide. The in vitro assay of chemically synthesized tREP-18 on the Ag83 strain of Leishmania donovani showed its potent antileishmanial property (IC50 value of 22.13 nM). The atomic force microscopy and scanning electron microscopy images indicated significant alteration in the cytoskeletal architecture of tREP-18-treated parasites. Also, tREP-18 seems to destabilize the mitochondrial membrane potential of parasites, disrupting their cellular integrity and leading to parasitic death. The cellular assays of the tREP-18 peptide on the BS12 strain, a clinical isolate of post-kala azar dermal leishmaniasis, demonstrated its significant efficacy at an IC50 value of 15 nM. The tREP-18 peptide showed a toxic effect on the amastigote stage of the parasite, showing macrophage pathogen clearance at a concentration of 22.5 nM. This study provides the proof of the concept of making a new class of functional peptides from tRNA sequences. It also opens a huge untapped tRNA-peptide space toward novel discoveries and applications. In the future, it would be interesting to perform tREP edits and redesign tREPs toward specific applications. © 2022 The Authors.

ACS Omega

tREPsâ"€A New Class of Functional tRNA-Encoded Peptides

Introduction: Metabolic Syndrome (MetS) constitutes an important risk factor for Alzheimer’s disease (AD); however, the mechanism linking these two disorders has not been completely elucidated. Hence, hypercoagulation may account for the missing hallmark connecting MetS and AD. The present review proposes how hemostatic imbalance triggered in MetS advances in the context of AD. MetS causes interruption of insulin signaling and inflammation, inciting insulin resistance in the brain. Subsequently, neuroinflammation and brain endothelial dysfunction are prompted that further intensify the exorbitant infiltration of circulating lipids and platelet aggregation, thereby causing hypercoagulable state, impairing fibrinolysis and eventually inducing prothrombic state in the brain leading to neurodegeneration. Objective: This study aims to understand the role of hypercoagulation in triggering the progression of neurodegeneration in MetS. It also offers a few interventions to prevent the progression of AD in MetS targeting hypercoagulation. Methods: Literature studies based on MetS related neurodegeneration, the impact of coagulation on aggravating obesity and AD via the mechanisms of BBB disruption, neuroinflammation, and hypofibrinolysis. Conclusion: The present paper proposes the hypothesis that hypercoagulation might amplify MetS associated insulin resistance, neuroinflammation, BBB disruption, and amyloid beta accumulation which eventually leads to AD. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

International Journal of Obesity

Targeting hypercoagulation to alleviate Alzheimer’s disease progression in metabolic syndrome

Drug resistance mutations of hepatitis C virus (HCV) negatively impact viral replicative fitness. RNA viruses are known to change their replication behaviour when subjected to suboptimal selection pressure. Here, we assess whether mutation supply in HCV is sufficiently large to allow the selection of its variants during dual or triple direct-acting antiviral (DAA) treatment associated with augmented virus fitness or impairment. We engineered randomly mutagenized full-genome libraries to create a highly diverse population of replication-competent HCV variants in cell culture. These variants exhibited escape when treated with NS5A/NS5B inhibitors (daclatasvir/sofosbuvir), and relapse on treatment with a combination of NS3/NS5A/NS5B inhibitors (simeprevir or paritaprevir/daclatasvir/sofosbuvir). Analysis of the relationship between virus fitness and drug resistance of JFH1-derived NS5A-5B variants showed a significant positive correlation (P=0.003). At the earliest time points, intracellular RNA levels remain unchanged in both the subgenomic replicon and infection assays, whereas extracellular RNA levels increased upto ten-fold compared to wild-type JFH1. Beneficial substitutions hyperstimulated phosphatidylinositol 4-phosphate during DAA treatment, and showed decreased dependence on cyclophilins during cyclosporine A treatment, indicating an interplay of virus-host molecular mechanisms in beneficial substitution selection that may necessitate infectious virus production. This comprehensive study demonstrates a possible role for HCV fitness of overcoming drug-mediated selection pressure. © 2022 Microbiology Society. All rights reserved.