Publications by authors named "Meenakshi Chaudhary"

11 Publications

  • Page 1 of 1

identification and validation of natural antiviral compounds as potential inhibitors of SARS-CoV-2 methyltransferase.

J Biomol Struct Dyn 2021 Feb 15:1-11. Epub 2021 Feb 15.

School of Biotechnology, Gautam Buddha University, Greater Noida, India.

The novel Coronavirus disease 2019 (COVID-19) is potentially fatal and caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Due to the unavailability of any proven treatment or vaccination, the outbreak of COVID-19 is wreaking havoc worldwide. Hence, there is an urgent need for therapeutics targeting SARS-CoV-2. Since, botanicals are an important resource for several efficacious antiviral agents, natural compounds gaining significant attention for COVID-19 treatment. In the present study, methyltranferase (MTase) of the SARS-CoV-2 is targeted using computational approach. The compounds were identified using molecular docking, virtual screening and molecular dynamics simulation studies. The binding mechanism of each compound was analyzed considering the stability and energetic parameter using methods. We have found four natural antiviral compounds Amentoflavone, Baicalin, Daidzin and Luteoloside as strong inhibitors of methyltranferase of SARS-CoV-2. ADMET prediction and target analysis of the selected compounds showed favorable results. MD simulation was performed for four top-scored molecules to analyze the stability, binding mechanism and energy requirements. MD simulation studies indicated energetically favorable complex formation between MTase and the selected antiviral compounds. Furthermore, the structural effects on these substitutions were analyzed using the principles of each trajectories, which validated the interaction studies. Our analysis suggests that there is a very high probability that these compounds may have a good potential to inhibit Methyltransferase (MTase) of SARS-CoV-2 and to be used in the treatment of COVID-19. Further studies on these natural compounds may offer a quick therapeutic choice to treat COVID-19. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1886174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885726PMC
February 2021

Baseline characterization of sediments and marine biota near industrial effluent discharge in Northumberland Strait, Nova Scotia, Canada.

Mar Pollut Bull 2020 Aug 13;157:111372. Epub 2020 Jun 13.

Cape Breton University, NS, Canada.

A bleached kraft pulp mill operating in Nova Scotia, Canada has discharged effluent into a former tidal estuary known as Boat Harbour since 1967. After treatment in Boat Harbour, effluent is discharged into Northumberland Strait. Contaminated sediments in Boat Harbour are slated for remediation following cessation of effluent discharge. A review of historical documents to identify contaminants in marine biota in Northumberland Strait found insufficient data to properly assess baseline conditions prior to remediation. This study measured metal, methylmercury, dioxin and furan concentrations in surficial sediments and American lobster (Homarus americanus), rock crabs (Cancer irroratus) and blue mussels (Mytilus edulis) in Northumberland Strait. When compared to Canadian Council of Ministers of the Environment sediment quality guidelines and Canadian Food Inspection Agency tissue guidelines results indicated limited contamination in sediments and biota, posing low risk to marine biota. Long-term monitoring is recommended to verify effectiveness of remediation.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111372DOI Listing
August 2020

Hepatitis E Virus Cysteine Protease Has Papain Like Properties Validated by Modeling and Cell-Free Inhibition Assays.

Front Cell Infect Microbiol 2019 23;9:478. Epub 2020 Jan 23.

Virology Lab, Department of Life Sciences, Shiv Nadar University, Greater Noida, India.

Hepatitis E virus (HEV) has emerged as a global health concern during the last decade. In spite of a high mortality rate in pregnant women with fulminant hepatitis, no antiviral drugs or licensed vaccine is available in India. HEV-protease is a pivotal enzyme responsible for ORF1 polyprotein processing leading to cleavage of the non-structural enzymes involved in virus replication. HEV-protease region encoding 432-592 amino acids of Genotype-1 was amplified, expressed in Sf21 cells and purified in its native form. The recombinant enzyme was biochemically characterized using SDS-PAGE, Western blotting and Immunofluorescence. The enzyme activity and the inhibition studies were conducted using Zymography, FTC-casein based protease assay and ORF1 polyprotein digestion. To conduct ORF1 digestion assay, the polyprotein, natural substrate of HEV-protease, was expressed in and purified. Cleavage of 186 kDa ORF1 polyprotein by the recombinant HEV-protease lead to appearance of non-structural proteins viz. Methyltransferase, Protease, Helicase and RNA dependent RNA polymerase which were confirmed through immunoblotting using antibodies generated against specific epitopes of the enzymes. FTC-casein substrate was used for kinetic studies to determine Km and Vmax of the enzyme and also the effect of different metal ions and other protease inhibitors. A 95% inhibition was observed with E-64 which was validated through analysis. The correlation coefficient between inhibition and docking score of Inhibitors was found to have a significant value of = 0.75. The predicted 3D model showed two domain architecture structures similar to Papain like cysteine protease though they differed in arrangements of alpha helices and beta sheets. Hence, we propose that HEV-protease has characteristics of "Papain-like cysteine protease," as determined through structural homology, active site residues and class-specific inhibition. However, conclusive nature of the enzyme remains to be established.
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http://dx.doi.org/10.3389/fcimb.2019.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989534PMC
September 2020

identification and evaluation of cold shock protein B (cspB)-like plant RNA chaperones.

J Biomol Struct Dyn 2021 Feb 12;39(3):841-850. Epub 2020 Feb 12.

School of Biotechnology, Gautam Buddha University, Greater Noida, India.

Cold shock domain (CSD) proteins with nucleic acid binding properties are well conserved from bacteria to higher organisms. In bacteria, the cold shock proteins (CSPs) are single domain RNA chaperones, whereas in animals and plants, CSDs are accompanied by additional domains with roles in transcription regulation. Bacterial CSPs (-cspA and -cspB) have successfully imparted drought tolerance in transgenic plants; however, these cannot be deployed in food crops due to their low public acceptance of transgenics with bacterial genes. Therefore, this study aimed to identify CSPB-like proteins from plants that can be used for developing drought tolerant transgenic crops. Twelve single domain plant CSPs presenting >40% sequence identity with CSPB were identified. All 12 plant CSPs were modeled by homology modeling and refined by molecular dynamics simulation for 10 ns. Selected plant CSPs and CSPB exhibited high structural similarity (Tm-score: 0.63-0.86). Structure based phylogenetic analysis revealed that csp1 and cspE are structurally closer to CSPB compared to their orthologs and paralogs. Molecular docking with three RNA molecules (5U, UC3U, and C2UC) indicates that csd1 and csp1 have a binding pattern and docking scores similar to those of CSPB. Furthermore, MD simulations for 20 ns and analysis of RMSD, RMSF, Rg as well as the number of hydrogen bonds in all the three complexes revealed that plant CSP-RNA complexes behave in a similar manner to that of the CSPB-RNA complex, making them highly potential candidate genes for developing drought tolerance in transgenic plants. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1719198DOI Listing
February 2021

Baseline assessment of contaminants in marine biota prior to remediation of industrial effluent impacted sediments in a former tidal estuary in Nova Scotia, Canada.

Mar Pollut Bull 2019 Aug 3;145:641-648. Epub 2019 Jul 3.

School for Resource and Environmental Studies, Dalhousie University, Halifax, NS, Canada. Electronic address:

Contaminated sediments at a pulp mill and former chor-alkali effluent treatment facility in Nova Scotia, Canada will undergo remediation. However, baseline studies assessing contaminants in marine biota in the marine receiving environment are lacking. Historical qualitative and quantitative contaminant data in biota from Boat Harbour (a former tidal lagoon which was used to treat industrial effluent since 1967), and surrounding marine environment were reviewed to establish baseline pollution from industrial effluent and contaminated sediments. Elevated metal, dioxins and furan concentrations previously measured in marine biota needs updating to help inform pre-remediation monitoring. Selection of species, contaminants of concern and sampling locations were ad hoc and often inconsistent with environmental effects monitoring requirements under Canadian federal Pulp and Paper Effluent Regulations. These consolidated baseline data are required to determine historical impacts and to assist future monitoring during Boat Harbour sediment remediation to compare against.
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http://dx.doi.org/10.1016/j.marpolbul.2019.06.055DOI Listing
August 2019

River Ganga pollution: Causes and failed management plans (correspondence on Dwivedi et al. 2018. Ganga water pollution: A potential health threat to inhabitants of Ganga basin. Environment International 117, 327-338).

Environ Int 2019 05 22;126:202-206. Epub 2019 Feb 22.

School for Resource and Environmental Studies, Dalhousie University, Halifax, NS B3H 4R2, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2019.02.033DOI Listing
May 2019

Reducing marine pollution from single-use plastics (SUPs): A review.

Mar Pollut Bull 2018 Dec 12;137:157-171. Epub 2018 Oct 12.

School for Resource and Environmental Studies, Dalhousie University, Halifax, NS, Canada. Electronic address:

Single-use plastics, or SUPs (plastic bags, microbeads, cutlery, straws and polystyrene) are substantial sources of plastic marine pollution, yet preventable via legislative and non-legislative interventions. Various international legislative strategies have been reported to address plastic marine pollution from plastic bags and microbeads, but these have since been accompanied by recent increasing public awareness triggered by international agencies and organizations. The Sixth International Marine Debris Conference highlighted increasing intervention strategies to mitigate SUP pollution. This study presents new multi-jurisdictional legislative interventions to reduce SUPs since 2017 and incorporates emergence of new non-legislative interventions to mitigate other types of SUPs at individual and private-sector levels that complement or influence legislative interventions. Further, effectiveness of SUP bag interventions (e.g., bans vs. levies) to help reduce SUP marine pollution are presented and range between 33 and 96% reduction in bag use.
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http://dx.doi.org/10.1016/j.marpolbul.2018.10.001DOI Listing
December 2018

Screening and In Vitro Evaluation of Potential Plasmodium falciparum Leucyl Aminopeptidase Inhibitors.

Curr Comput Aided Drug Des 2016 ;12(4):282-293

School of Biotechnology, Gautam Buddha University, Greater Noida, 201312, India.

Background: Plasmodium falciparum leucyl aminopeptidase (PfA-M17) regulates the intracellular pool of amino acids required for the growth and development of parasites. Thus, PfA-M17 is a promising target for anti-malarial drug development.

Method: In the present study, structure-based drug design was used to identify novel PfA-M17 inhibitors, which were subsequently validated by in vitro PfA-M17 and human LAP3 enzyme inhibition assay. A library of 3,147,882 compounds was screened using receptor-based virtual screening against the active site of PfA-M17, and three levels of accuracy were used: high-throughput virtual screening, gridbased ligand docking with energetics (Glide standard precision) and Glide extra precision.

Results: Seventeen screened compounds were selected and tested in the rPfA-M17 enzyme inhibition assay. Of these nine compounds were found to be effective inhibitors. To test the target activity, all nine PfA-M17 inhibitors were tested against rhLAP3, the human homolog of PfA-M17. One compound (compound 2) was found to be moderately effective against PfA-M17 (Ki = 287 μM) with limited inhibitory activity against hLAP3 (Ki of 4,464 μM). Subsequently, induced fit docking and pharmacophore modelling were used to further understand more precise ligand-protein interactions in the protein-inhibitor complexes.

Conclusion: Among the 9 effective PfA-M17 inhibitors, 5 compounds were found effective in the P. falciparum schizont maturation inhibition (SMI) assay. A good correlation (r =0.83) was observed between the rPfA-M17 enzyme inhibition concentration and SMI assay.
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http://dx.doi.org/10.2174/1573409912666160722111053DOI Listing
February 2017

Oral Manifestations and Molecular Basis of Oral Genodermatoses: A Review.

J Clin Diagn Res 2016 May 1;10(5):ZE08-12. Epub 2016 May 1.

Research Scientist, Rajiv Gandhi Cancer Institute , Delhi, India .

Genodermatoses refers to group of inherited monogenic disorders with skin manifestations. Many of these disorders are rare and also have oral manifestations, called oral genodermatoses. This article provides a focused review of molecular basis of important genodermatoses that affects the oral cavity and also have prominent associated dermatologic features. In several conditions discussed here, the oral findings are distinct and may provide the first clue of an underlying genetic diagnosis. The article also emphasises on the prenatal diagnosis, genetic counselling and the treatment oral genodermatoses.
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http://dx.doi.org/10.7860/JCDR/2016/17647.7751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948553PMC
May 2016

Modelling of human leucyl aminopeptidases for in silico off target binding analysis of potential Plasmodium falciparum leucine aminopeptidase (PfA-M17) specific inhibitors.

Recent Pat Endocr Metab Immune Drug Discov 2014 ;8(3):191-201

School of Biotechnology, Gautam Buddha University, Greater NOIDA, 201312, India.

Malaria is one of the most widespread infectious diseases in the world. Emergence of multi-drug resistant Plasmodium strains makes it crucial to identify new classes of compounds for anti-malarial therapy. Novel anti-malarial compounds from natural sources (Gomphostema niveum) as well as synthetic chemicals (5-aminolevulinic acid) have been reported in recent patents. Plasmodium falciparum leucyl aminopeptidase (PfA-M17) is a validated target for antimalarial drug development. However, known aminopeptidase inhibitors beset with the problem of non-specificity. Therefore, 3D structural models of PfA-M17 human homologs, Leucine aminopeptidase3 (hLAP3) and probable leucine aminopeptidase (hNPEPL1) were predicted for molecular docking based screening of potential inhibitors for their off target activity. Comparison of IC50 and docking scores of highly active hLAP3 inhibitors shows good correlation (r(2)≈ 0.8). Further, docking analysis with potential PfA-M17 inhibitor Compound-X (identified through virtual screening) shows much higher binding affinity towards PfA-M17 (docking score -11.44) than hLAP3 (docking score -4.26) and hNPEPL1 (docking score -5.08). This lead compound, Compound-X can act as a scaffold for further increasing PfA-M17 binding affinity and hLAP3 and hNPEPL1 3D structure models will be useful for screening of PfA-M17 specific inhibitors.
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http://dx.doi.org/10.2174/1872214808666141001125057DOI Listing
September 2015

Modeling of human M1 aminopeptidases for in silico screening of potential Plasmodium falciparum alanine aminopeptidase (PfA-M1) specific inhibitors.

Bioinformation 2014 30;10(8):518-25. Epub 2014 Aug 30.

School of Biotechnology, Gautam Buddha University, Greater Noida, 201312, India.

Plasmodium falciparum alanine M1-aminopeptidase (PfA-M1) is a validated target for anti-malarial drug development. Presence of significant similarity between PfA-M1 and human M1-aminopeptidases, particularly within regions of enzyme active site leads to problem of non-specificity and off-target binding for known aminopeptidase inhibitors. Molecular docking based in silico screening approach for off-target binding has high potential but requires 3D-structure of all human M1-aminopeptidaes. Therefore, in the present study 3D structural models of seven human M1-aminopeptidases were developed. The robustness of docking parameters and quality of predicted human M1-aminopeptidases structural models was evaluated by stereochemical analysis and docking of their respective known inhibitors. The docking scores were in agreement with the inhibitory concentrations elucidated in enzyme assays of respective inhibitor enzyme combinations (r2≈0.70). Further docking analysis of fifteen potential PfA-M1 inhibitors (virtual screening identified) showed that three compounds had less docking affinity for human M1-aminopeptidases as compared to PfA-M1. These three identified potential lead compounds can be validated with enzyme assays and used as a scaffold for designing of new compounds with increased specificity towards PfA-M1.
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http://dx.doi.org/10.6026/97320630010518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166772PMC
September 2014