Life Sciences

<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

<p>Nematode parasites of the family Anisakidae infect definitive hosts, such as fish-eating birds and mammals, through primary intermediate hosts like copepods and secondary intermediate hosts like fishes. However, consumption of raw or undercooked fish can lead to nematode infection called anisakidosis in humans. We observed the presence of nematode infection in hillstream loaches of families Cobitidae and Nemacheilidae available for human consumption in the local markets in the northern parts of Western Ghats, India. Scanning electron micrograph and genetic identification employing mitochondrial cytochrome oxidase subunit II, identified the nematode to the genus Contracaecum. Histology of infected host revealed the presence of the parasite in muscles. Antioxidant enzyme analysis of host liver suggested that infection leads to oxidative stress in the fish. We suspect that a gradual increase in parasite infection of the loaches in the last decade could be attributed to various anthropogenic stressors that are altering riverine habitats. Since loaches are consumed by tribal people who often prepare the fish without degutting and possibly undercooked, there is a potential threat of human infection. © 2022 John Wiley &amp; Sons Ltd.</p>

World University root node

(SoNS) School of Natural Sciences

Journal of Fish Diseases

Contracaecum nematode parasites in hillstream loaches of the Western Ghats, India

The lack of a convenient method for the iterative generation of diverse full-length viral variants has impeded the study of directed evolution in RNA viruses. By integrating a full RNA genome error-prone PCR and reverse genetics, random genome-wide substitution mutagenesis can be induced. We have developed a method using this technique to synthesize diverse libraries to identify viral mutants with phenotypes of interest. This method, called full-length mutant RNA synthesis (FL-MRS), offers the following advantages: (i) the ability to create a large library via a highly efficient one-step error-prone PCR; (ii) the ability to create groups of libraries with varying levels of genetic diversity by manipulating the fidelity of DNA polymerase; (iii) the creation of a full-length PCR product that can directly serve as a template for mutant RNA synthesis; and (iv) the ability to create RNA that can be delivered into host cells as a non-selected input pool to screen for viral mutants of the desired phenotype. We have found, using a reverse genetics approach, that FL-MRS is a reliable tool to study viral-directed evolution at all stages in the life cycle of the hepatitis C virus, JFH1 isolate. This technique appears to be an invaluable tool to employ directed evolution to understand adaptation, replication, and the role of viral genes in pathogenesis and antiviral resistance in positive-sense RNA viruses. © 2022, Journal of Visualized Experiments. All rights reserved.

Journal of Visualized Experiments

Reverse Genetics to Engineer Positive-sense RNA Virus Variants

In order to survive and establish infection, the Plasmodium parasite employs various strategies to evade the host immune response. The var genes family, a repertoire of 60 genes, expresses parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocytes, and by continuously switching the variants of PfEMP1, help the parasite to avoid detection and destruction by the host immune system during the intra-erythrocytic developmental cycle. Although chromatin modifications are recognised to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, the precise histone codes and molecular players and mechanisms guiding these modifications have yet to be unravelled in depth. In this study, we have functionally characterised RUVBL proteins of Plasmodium falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in the ring stage of the parasite. Further, we have demonstrated that the PfMYST/PfRUVBL complex interacts with core histones, H3 and H4. Overall the findings of this study add further information by identifying the potential role of epigenetic regulators, PfMYST and PfRUVBL, in the regulation of monoallelic expression of var genes in the malaria parasite. © The Author(s) 2022.

Pathogens and Disease

Plasmodium falciparum PfRUVBL proteins bind at the TARE region and var gene promoter located in the subtelomeric region

Removal of heavy metals (Cd and Cr) from industrial wastewater by adsorption onto a series of Ca substituted nickel zinc nanoferrites (CaxNi0.4Zn0.6-xFe2O4 (x = 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6)) (CNZNFs) was studied in detail. The effect of calcium doping and contact time over adsorption of cadmium and chromium ions was investigated and maximum uptake of Cd (98.25%) and Cr (51%) ions were marked by prepared nanoadsorbents. Structural studies confirmed the formation of spinel structured nanoparticles with crystallite size ranging from 24 to 38 nm while porosity was observed to vary from 52% to 58% with calcium concentration. Pseudo second order (PSO) kinetic model for adsorption of both heavy metals (cadmium and chromium) was observed to be better fitted with adsorption data. Maximum adsorption efficiencies for Cd (128.20 mg/g) and Cr (23.54 mg/g) were found by the data fit of Langmuir isotherm model. Additionally, the adsorption data was found to obey Langmuir isotherm model for both heavy metals due to higher values of correlation coefficients (R2 = 0.94131 for cadmium and 0.91091 for chromium) than Freundlich isotherm model (R2 = 0.5865 for cadmium and 0.4599 for chromium). © 2022 Elsevier Ltd and Techna Group S.r.l.

Ceramics International

Adsorption of Cd and Cr ions from industrial wastewater using Ca doped Ni–Zn nanoferrites: Synthesis, characterization and isotherm analysis

Fulltext

Frontiers in Microbiology

Editorial: Plastic to Bioplastic (P2BP): A Green Technology for Circular Bioeconomy

Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during Plasmodium falciparum invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein–protein interaction (PPI) network-based molecular machinery. Here, we used an integrated in silico analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in P. falciparum, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP’s interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed via synergistic inhibition in P. falciparum invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion via glideosome assembly protein myosin A in P. falciparum. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics. Copyright © 2022 Anam, Kumari, Mukherjee, Rex, Biswas, Maurya, Ravikumar, Gupta, Kushawaha, Sah, Chaurasiya, Singhal, Singh, Kaushik, Prasad, Pati, Ranganathan and Singh.

Frontiers in Cellular and Infection Microbiology

Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients. © 2022 Future Medicine Ltd.

Future Microbiology

G6PD deficiency: imbalance of functional dichotomy contributing to the severity of COVID-19

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.

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.

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