Skrining Senyawa dari Tanaman Rhodomyrtus tomentosa (Aiton) Hassk terhadap SARS-CoV-2 ORF3a

The ORF3a protein from SARS-CoV has functions in terms of ion channel activity, modulates the trafficking properties of SARS-CoV spike (S) protein, increases fibrinogen expression in pulmonary epithelial cells, and induces apoptosis. So that research is needed to overcome the ORF3a experiment. The method in this research uses the computational screening method with autodok4 software. The results of this study resulted in free binding energy between Hassk Rhodomyrtus tomentosa (Aiton) and ORF3a compounds, namely: α-tocopherol-quinone (-5.86); blumeatin (-4.98); methyl cinnamate (-4.44); myricetin (-4.49); naringenin (-4.93); quercetin (-4,9); rhodomyrtone (-6); rhodomyrtosone B (-7.11); rhodomyrtosone C (-6.77); tetrahydroxyflavanone (-4.91); α-tocopherol A (-6.72); verimol K (-4.89); watsonianone A (-7.55). Based on the data obtained, the ligand with the most potential due to the stability of the bond is watsonianone A.

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In silico Study of Potential Non-oxime Reactivator for Sarin-inhibited Human Acetylcholinesterase

Pertanika Journal of Science and Technology ◽

10.47836/pjst.29.3.19 ◽

2021 ◽

Vol 29 (3) ◽

Author(s):

Rauda A. Mohamed ◽

Keat Khim Ong ◽

Norhana Abdul Halim ◽

Noor Azilah Mohd Kasim ◽

Siti Aminah Mohd Noor ◽

...

Keyword(s):

Binding Energy ◽

In Silico ◽

Docking Study ◽

Dynamics Simulation ◽

Nucleophilic Attack ◽

Organophosphate Poisoning ◽

Nipecotic Acid ◽

Computational Screening ◽

The Stability ◽

New Compounds

The search for new compounds other than oxime as potential reactivator that is effective upon organophosphate poisoning treatments is desired. The less efficacy of oxime treatment has been the core factor. Fourteen compounds have been screened via in silico approach for their potential as sarin-inhibited human acetylcholinesterase poisoning antidotes. The selection of the compounds to be synthesized based on this computational screening, reduces the time and cost needed. To perform the docking study of sarin-inhibited acetylcholinesterase and reactivator-sarin inhibited acetylcholinesterase complexations, a bioinformatics tool was used. Estimation of the nucleophilic attack distance and binding energy of fourteen potential compounds with sarin inhibited acetylcholinesterase complexes to determine their antidote capacities was carried out using Autodock. A commercially available antidote, 2-PAM was used for the comparison. The best docked-pose was further examined with molecular dynamics simulation. Apart from being lipophilic, a compound with a carboxylic acid, (R)-Boc-nipecotic acid is shown to exhibit 6.29 kcal/mol binding energy with 8.778 Å distance of nucleophilic attack. The stability and flexibility of the sarin-inhibited acetylcholinesterase, complexed with (R)-Boc-nipecotic acid suggests this compound should be tested experimentally as a new, promising antidote for sarin-inhibited acetylcholinesterase poisoning.

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Myrsinane and related diterpenes from Euphorbia falcata with selective potassium ion channel activity

Planta Medica ◽

10.1055/s-0035-1565539 ◽

2015 ◽

Vol 81 (16) ◽

Author(s):

A Vasas ◽

P Orvos ◽

L Tálosi ◽

P Forgo ◽

G Pinke ◽

...

Keyword(s):

Ion Channel ◽

Potassium Ion ◽

Channel Activity ◽

Potassium Ion Channel

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Destabilizing the Structural Integrity of SARS-CoV2 Receptor Proteins by Curcumin Along with Hydroxychloroquine: An Insilco Approach for a Combination Therapy

10.26434/chemrxiv.12090438.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Akhileshwar Srivastava ◽

Divya Singh

Keyword(s):

Binding Energy ◽

Combination Therapy ◽

Receptor Binding ◽

Structural Integrity ◽

Binding Domain ◽

Receptor Binding Domain ◽

Receptor Proteins ◽

Main Protease ◽

The Stability ◽

Therapeutic Activities

Presently, an emerging disease (COVID-19) has been spreading across the world due to coronavirus (SARS-CoV2). For treatment of SARS-CoV2 infection, currently hydroxychloroquine has been suggested by researchers, but it has not been found enough effective against this virus. The present study based on in silico approaches was designed to enhance the therapeutic activities of hydroxychloroquine by using curcumin as an adjunct drug against SARS-CoV2 receptor proteins: main-protease and S1 receptor binding domain (RBD). The webserver (ANCHOR) showed the higher protein stability for both receptors with disordered score (<0.5). The molecular docking analysis revealed that the binding energy (-24.58 kcal/mol) of hydroxychloroquine was higher than curcumin (-20.47 kcal/mol) for receptor main-protease, whereas binding energy of curcumin (<a>-38.84</a> kcal/mol) had greater than hydroxychloroquine<a> (-35.87</a> kcal/mol) in case of S1 receptor binding domain. Therefore, this study suggested that the curcumin could be used as combination therapy along with hydroxychloroquine for disrupting the stability of SARS-CoV2 receptor proteins

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Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

Current Computer - Aided Drug Design ◽

10.2174/1573409914666180629151906 ◽

2018 ◽

Vol 15 (1) ◽

pp. 82-88 ◽

Cited By ~ 1

Author(s):

Md. Mostafijur Rahman ◽

Md. Bayejid Hosen ◽

M. Zakir Hossain Howlader ◽

Yearul Kabir

Keyword(s):

Binding Energy ◽

Middle East ◽

Virtual Screening ◽

In Silico ◽

Screening Method ◽

Middle East Respiratory Syndrome ◽

Cytochrome P450 Enzymes ◽

Drug Molecules ◽

Essential Enzyme ◽

Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

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Hierarchical computational screening of layered lead-free metal halide perovskites for optoelectronic applications

Journal of Materials Chemistry A ◽

10.1039/d0ta10098f ◽

2021 ◽

Author(s):

Qiuqi Li ◽

Dan Cao ◽

Xueyin Liu ◽

Xiangyu Zhou ◽

Xiaoshuang Chen ◽

...

Keyword(s):

High Stability ◽

Screening Method ◽

Optoelectronic Properties ◽

Metal Halide ◽

Lead Free ◽

Computational Screening ◽

Halide Perovskites ◽

Optoelectronic Applications ◽

Free Metal

A hierarchical computational screening method is used to find layered lead-free metal halide perovskites with high stability and outstanding optoelectronic properties.

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Neuromuscular junction-specific genes screening by deep RNA-seq analysis

Cell & Bioscience ◽

10.1186/s13578-021-00590-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiankun Hui ◽

Hongyang Jing ◽

Xinsheng Lai

Keyword(s):

Ion Channel ◽

Neuromuscular Junctions ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Muscle Membrane ◽

Receptor Interaction ◽

Specific Gene ◽

Rna Seq ◽

Channel Activity ◽

Ppi Networks

Abstract Background Neuromuscular junctions (NMJs) are chemical synapses formed between motor neurons and skeletal muscle fibers and are essential for controlling muscle contraction. NMJ dysfunction causes motor disorders, muscle wasting, and even breathing difficulties. Increasing evidence suggests that many NMJ disorders are closely related to alterations in specific gene products that are highly concentrated in the synaptic region of the muscle. However, many of these proteins are still undiscovered. Thus, screening for NMJ-specific proteins is essential for studying NMJ and the pathogenesis of NMJ diseases. Results In this study, synaptic regions (SRs) and nonsynaptic regions (NSRs) of diaphragm samples from newborn (P0) and adult (3-month-old) mice were used for RNA-seq. A total of 92 and 182 genes were identified as differentially expressed between the SR and NSR in newborn and adult mice, respectively. Meanwhile, a total of 1563 genes were identified as differentially expressed between the newborn SR and adult SR. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) of the DEGs were performed. Protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape. Further analysis identified some novel proteins and pathways that may be important for NMJ development, maintenance and maturation. Specifically, Sv2b, Ptgir, Gabrb3, P2rx3, Dlgap1 and Rims1 may play roles in NMJ development. Hcn1 may localize to the muscle membrane to regulate NMJ maintenance. Trim63, Fbxo32 and several Asb family proteins may regulate muscle developmental-related processes. Conclusion Here, we present a complete dataset describing the spatiotemporal transcriptome changes in synaptic genes and important synaptic pathways. The neuronal projection-related pathway, ion channel activity and neuroactive ligand-receptor interaction pathway are important for NMJ development. The myelination and voltage-gated ion channel activity pathway may be important for NMJ maintenance. These data will facilitate the understanding of the molecular mechanisms underlying the development and maintenance of NMJ and the pathogenesis of NMJ disorders.

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