A method to increase line-density of grating based on PDMS stretching and PUA replication process

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

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Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999201110204116 ◽

2020 ◽

Vol 21 ◽

Author(s):

Acharya Balkrishna ◽

Rashmi Mittal ◽

Vedpriya Arya

Keyword(s):

Molecular Docking ◽

Md Simulation ◽

Bond Distance ◽

Immunological Response ◽

Docking Study ◽

Receptor Interaction ◽

Molecular Docking Study ◽

Replication Process ◽

Stable Conformation ◽

Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

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Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200923143935 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bichismita Sahu ◽

Santosh Kumar Behera ◽

Rudradip Das ◽

Tanay Dalvi ◽

Arnab Chowdhury ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Peptide Nucleic Acid ◽

Large Set ◽

Nonstructural Proteins ◽

In Silico Screening ◽

Replication Process ◽

Enveloped Virus ◽

Treatment Regimens ◽

Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

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Coronavirus: history, genome structure and pathogenesis

Coronaviruses ◽

10.2174/2666796701999200918160354 ◽

2020 ◽

Vol 01 ◽

Author(s):

Poonam B ◽

Prabhjot Kaur Gill

Keyword(s):

Genome Structure ◽

Public Health Research ◽

Replication Process ◽

Virus Family ◽

Enveloped Virus ◽

Target Organs ◽

Transcription Process ◽

Recent Emergence ◽

The Family ◽

Discontinuous Transcription

Background: The positive sense and inordinate large RNA genome are enclosed by helical nuceocapsids along with an outermost layer belongs to the family Coronaviridae. The phylogenetic tree of this family has been quartered into Class1 as alpha, Class 2 as beta, Class 3 as gamma and Class 4 as delta CoV. The mammalian respiratory and gastrointestinal tracts are the main target organs of this enveloped virus with misperceived mechanisms. The relevance of this virus family has considerably increased by the dint of recent emergence of the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), which are caused by viruses belonging to the beta-CoV group. Aim: Aforesaid illustrations of emergence of coronavirus diseases over the past two decades, SARS (2002 and 2003) and MERS (2012 to present) - the ongoing COVID-19 outbreak has pressurized the WHO to take innovative measures for public health, research and medical communities. The aim of the present review is to have proficiency in coronavirus replication and transcription process which is still in its infancy. Conclusion: An outcome of epidemics, it is being recognized as one of the most advancing viruses by the virtue of high genomic nucleotide substitution rates and recombination. The hallmark of coronavirus replication is discontinuous transcription resulting in the production of multiple subgenomic mRNAs having sequences complementary to both ends of the genome. Therefore, complete genome sequence of coronavirus will be used as frame of reference for knowing this classical phenomenon of RNA replication process. Finally, research on the pathogenesis of coronaviruses and the host immunopathological response will aid in designing vaccines and minimizing mortality rate.

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Replication process of the parvovirus H-1. VII. Electron microscopy of replicative-form DNA synthesis.

Journal of Virology ◽

10.1128/jvi.21.2.713-723.1977 ◽

1977 ◽

Vol 21 (2) ◽

pp. 713-723 ◽

Cited By ~ 4

Author(s):

I I Singer ◽

S L Rhode

Keyword(s):

Electron Microscopy ◽

Dna Synthesis ◽

Replicative Form ◽

Replication Process

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Biomimetic Approach for the Elaboration of Highly Hydrophobic Surfaces: Study of the Links between Morphology and Wettability

Biomimetics ◽

10.3390/biomimetics6020038 ◽

2021 ◽

Vol 6 (2) ◽

pp. 38

Author(s):

Quentin Legrand ◽

Stephane Benayoun ◽

Stephane Valette

Keyword(s):

Contact Angle ◽

Ginkgo Biloba ◽

Contact Angle Hysteresis ◽

Contact Angles ◽

Textured Surfaces ◽

Replication Process ◽

Wetting Behavior ◽

Static Contact ◽

Biomimetic Approach ◽

Highly Hydrophobic

This investigation of morphology-wetting links was performed using a biomimetic approach. Three natural leaves’ surfaces were studied: two bamboo varieties and Ginkgo Biloba. Multiscale surface topographies were analyzed by SEM observations, FFT, and Gaussian filtering. A PDMS replicating protocol of natural surfaces was proposed in order to study the purely morphological contribution to wetting. High static contact angles, close to 135∘, were measured on PDMS replicated surfaces. Compared to flat PDMS, the increase in static contact angle due to purely morphological contribution was around 20∘. Such an increase in contact angle was obtained despite loss of the nanometric scale during the replication process. Moreover, a significant decrease of the hysteresis contact angle was measured on PDMS replicas. The value of the contact angle hysteresis moved from 40∘ for flat PDMS to less than 10∘ for textured replicated surfaces. The wetting behavior of multiscale textured surfaces was then studied in the frame of the Wenzel and Cassie–Baxter models. Whereas the classical laws made it possible to describe the wetting behavior of the ginkgo biloba replications, a hierarchical model was developed to depict the wetting behavior of both bamboo species.

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Antiviral, Antibacterial, Antifungal, and Antiparasitic Properties of Propolis: A Review

Foods ◽

10.3390/foods10061360 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1360

Author(s):

Felix Zulhendri ◽

Kavita Chandrasekaran ◽

Magdalena Kowacz ◽

Munir Ravalia ◽

Krishna Kripal ◽

...

Keyword(s):

Clinical Trials ◽

Antioxidant Status ◽

Energy Production ◽

Mechanisms Of Action ◽

Host Cells ◽

Physical Barrier ◽

Inflammatory Signaling ◽

Replication Process ◽

Comprehensive Review ◽

Cellular Organelles

Propolis is a complex phytocompound made from resinous and balsamic material harvested by bees from flowers, branches, pollen, and tree exudates.Humans have used propolis therapeutically for centuries. The aim of this article is to provide comprehensive review of the antiviral, antibacterial, antifungal, and antiparasitic properties of propolis. The mechanisms of action of propolis are discussed. There are two distinct impacts with regards to antimicrobial and anti-parasitic properties of propolis, on the pathogens and on the host. With regards to the pathogens, propolis acts by disrupting the ability of the pathogens to invade the host cells by forming a physical barrier and inhibiting enzymes and proteins needed for invasion into the host cells. Propolis also inhibits the replication process of the pathogens. Moreover, propolis inhibits the metabolic processes of the pathogens by disrupting cellular organelles and components responsible for energy production. With regard to the host, propolis functions as an immunomodulator. It upregulates the innate immunity and modulates the inflammatory signaling pathways. Propolis also helps maintain the host’s cellular antioxidant status. More importantly, a small number of human clinical trials have demonstrated the efficacy and the safety of propolis as an adjuvant therapy for pathogenic infections.

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Mathematical Notes by Professor Tait (2.) On the Equipotential Surfaces for a Straight Wire

Proceedings of the Royal Society of Edinburgh ◽

10.1017/s0370164600052470 ◽

1875 ◽

Vol 8 ◽

pp. 443-443

Keyword(s):

Natural Philosophy ◽

Line Density ◽

Straight Wire ◽

Equipotential Surfaces ◽

The Wire ◽

Image Position

Some results given in Vol. I. of Thomson and Tait's Natural Philosophy may be much more simply obtained by calculating the potential of a wire rather than its attraction. That potential is easily found aswhere c is the length of the wire, ρ its line density, r1 and r2 the distances of its ends from the point at which the potential is to be found.

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