scholarly journals VIRTUAL SCREENING OF INDONESIAN HERBAL DATABASE FOR CP ALLOSTERIC MODULATOR OF HEPATITIS B VIRUS

2018 ◽  
Vol 10 (1) ◽  
pp. 190
Author(s):  
Ulfa Ivonie ◽  
Arry Yanuar ◽  
Firdayani .
Keyword(s):  
Virtual Screening ◽  
Core Protein ◽  
Area Under The Curve ◽  
Receiver Operating Characteristics ◽  
Screening Methods ◽  
Allosteric Modulator ◽  
Operating Characteristics ◽  
Autodock Vina ◽  
The Core ◽  
B Virus

Objective: This study performed a virtual screening of the Indonesian Herbal Database for the core protein allosteric modulator of the hepatitis Bvirus (HBV) using AutoDock and AutoDock Vina software, to discover novel safe drugs for patients.Methods: The method was validated using the parameters enrichment factor (EF), receiver operating characteristics, and area under the curve (AUC).The grid box size used in virtual screening with AutoDock was 55 × 55 × 55 with EF10% of 0.7652 and AUC of 0.6709, whereas that used in virtualscreening with AutoDock Vina was 20.625 × 20.625 × 20.625 with EF5% of 0.5075 and AUC of 0.7832.Results: The top 10 compounds from virtual screening with AutoDock at G levels −11.74–−10.31 kcal/mol were yuehchukene, lansionic acid, stigmast-4-en-3-one, myrtillin, sanggenol O, lanosterol, erycrista-gallin, alpha-spinasterol, cyanidin 3-arabinoside, and cathasterone and with AutoDock Vinaat G levels −12.1 to −10.7 kcal/mol were sanggenol O, cucumerin A, yuehchukene, palmarumycin CP1, dehydrocycloguanandin, myrtillin, liriodenine,myricetin 3-alpha-L-arabinopyranoside, myricetin 3-galactoside, and cassameridine.Conclusion: Three compounds were in top list of both virtual screening methods against Cp allosteric modulator of HBV are myrtillin, sanggenol O,and yuehchukene have a prospect to be investigated futher for anti HBV.

scholarly journals VIRTUAL SCREENING OF BETA-SECRETASE 1 (BACE1) INHIBITORS IN THE INDONESIAN HERBAL DATABASE AS USING AUTODOCK AND AUTODOCK VINA

2017 ◽  
Vol 10 (17) ◽  
pp. 148
Author(s):  
Asti Anna Tanisa ◽  
Rezi Riadhi
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Cellular Response ◽  
Senile Plaque ◽  
Area Under The Curve ◽  
Neuronal System ◽  
Operating Characteristics ◽  
Autodock Vina ◽  
Beta Secretase ◽  
The Brain

  Objective: Alzheimer’s is a neurodegenerative disease caused by the accumulation of senile plaque in the brain that affects neuronal system leading to a less sensitive cellular response from neurons. Previous research has found that beta-secretase 1 (BACE1) plays an important role in the senile plaque formation, become a target in Alzheimer’s medication.Methods: In this study, virtual screening of BACE1 inhibitors on the Indonesian Herbal Database was done using AutoDock and AutoDock Vina. The screening was validated using the directory of useful decoys: Enhanced database. Parameters for validation process of AutoDock and AutoDock Vina are enrichment factor (EF), receiver operating characteristics, and area under the curve (AUC).Results: The dimensions of grid boxes were 30×30×30 (AutoDock) and 11.25×11.25×11.25 (AutoDock Vina). The EF 1% and AUC values obtained from the AutoDock are 7.74 and 0.73, respectively, and in the AutoDock Vina are 4.6 and 0.77, respectively. Based on the virtual screening results, the top six compounds obtained using AutoDock (binding energy ranging from −7.84 kcal/mol to −8.79 kcal/mol) include: Azadiradione, cylindrin, lanosterol, sapogenin, simiarenol, and taraxerol. The top seven compounds (binding energy ranging from −8.8 kcal/mol to −9.4 kcal/mol) obtained using AutoDeck Vina include: Bryophyllin A, diosgenin, azadiradione, sojagol, beta-amyrin, epifriedelinol, and jasmolactone C.Conclusions: Only azadiradione was obtained from the virtual screening conducted using both types of software; it interacts with the active region in BACE1 at residue Trp 76 (AutoDock result) and Thr 232 (AutoDock Vina result).  

scholarly journals Hepatitis B viral core proteins with an N-terminal extension can assemble into core-like particles but cannot be enveloped

1999 ◽  
Vol 80 (10) ◽  
pp. 2647-2659 ◽  
Author(s):  
Eric Ka-Wai Hui ◽  
Yong Shyang Yi ◽  
Szecheng J. Lo
Keyword(s):  
Hepatitis B ◽  
Kinase Activity ◽  
Core Protein ◽  
Surface Antigens ◽  
Human Hepatoma Cells ◽  
The Core ◽  
Core Proteins ◽  
B Virus ◽  
Transfection Medium ◽  
Cscl Gradient

The structure of hepatitis B virus (HBV) nucleocapsids has been revealed in great detail by cryoelectron microscopy. How nucleocapsids interact with surface antigens to form enveloped virions remains unknown. In this study, core mutants with N-terminal additions were created to address two questions: (1) can these mutant core proteins still form nucleocapsids and (2) if so, can the mutant nucleocapsids interact with surface antigens to form virion-like particles. One plasmid encoding an extra stretch of 23 aa, including six histidine residues, fused to the N terminus of the core protein (designated HisC183) was expressed in Escherichia coli and detected by Western blot. CsCl gradient and electron microscopy analyses indicated that HisC183 could self-assemble into nucleocapsids. When HisC183 or another similar N-terminal fusion core protein (designated FlagC183) was co-expressed with a core-negative plasmid in human hepatoma cells, both mutant core proteins self-assembled into nucleocapsids. These particles also retained kinase activity. Using an endogenous polymerase assay, a fill-in HBV DNA labelled with isotope was obtained from intracellular nucleocapsids formed by mutant cores. In contrast, no such signal was detected from the transfection medium, which was consistent with PCR and Southern blot analyses. Results indicate that core mutants with N-terminal extensions can form nucleocapsids, but are blocked during the envelopment process and cannot form secreted virions. The mutant nucleocapsids generated from this work should facilitate further study on how nucleocapsids interact with surface antigens.

Sensitivity and specificity of Sirius indices in diagnosis of keratoconus and suspect keratoconus

2021 ◽  
pp. 112067212110601
Author(s):  
Abdelrahman Salman ◽  
Taym Darwish ◽  
Ali Ali ◽  
Marwan Ghabra ◽  
Rafea Shaaban
Keyword(s):  
Sensitivity And Specificity ◽  
Predictive Accuracy ◽  
Corneal Thickness ◽  
Case Series ◽  
Area Under The Curve ◽  
Receiver Operating Characteristics ◽  
Operating Characteristics ◽  
Symmetry Index ◽  
Case Series Study ◽  
Receiver Operating

Aim To estimate the sensitivity and specificity of topographic and tomographic corneal parameters as determined by Sirius (CSO, Florence, Italy) in discriminating keratoconus (KC) and suspect keratoconus from normal cornea. Method In this retrospective case-series study, keratoconus screening indices were measured using Sirius tomographer. Receiver operating characteristics (ROC) curves were used to determine the test's overall predictive accuracy (area under the curve) and to identify optimal cut-off points to maximize sensitivity and specificity in differentiating keratoconus and suspect keratoconus from normal corneas. Results Receiver operating characteristics (ROC) curve analyses showed high predictive accuracy for Symmetry Index back (SIb), Keratoconus Vertex front (KVf), Symmetry Index front (SIf), Keratoconus Vertex back (KVb), Apex Keratometry (Curve-Apex) and Minimum corneal Thickness (ThkMin) to distinguish keratoconus from normal (area under the curve > 0.9, all). Symmetry Index back was identified as the best diagnostic parameter for detecting suspect keratoconus with AUC of 0.86. Highest specificity to detect keratoconus and suspect keratoconus was seen for SIb, 99.87% and 84.66%, respectively. These values were associated with optimal cut-off points of 0.46 D for keratoconus and 0.12 D for suspect keratoconus. Conclusion Sirius parameters evaluated in the study were effective to differentiate keratoconus from normal corneas. However, Symmetry Index back was the index with the highest ability to detect suspect keratoconus.

scholarly journals Urine α-fetoprotein and orosomucoid 1 as biomarkers of hepatitis B virus-associated hepatocellular carcinoma

2020 ◽  
Vol 318 (2) ◽  
pp. G305-G312 ◽  
Author(s):  
Zhu Zhan ◽  
Yalan Guan ◽  
Kenley Mew ◽  
Weiqiong Zeng ◽  
Mingli Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Area Under The Curve ◽  
Screening Methods ◽  
Diagnostic Analysis ◽  
B Virus ◽  
New Perspective ◽  
Urine Reagent Strips ◽  
Better Than

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort ( n = 40). The selected proteins were confirmed using ELISA in a validation cohort ( n = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson’s r = 0.944, P < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result. NEW & NOTEWORTHY This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.

scholarly journals Does a cdc2 Kinase-Like Recognition Motif on the Core Protein of Hepadnaviruses Regulate Assembly and Disintegration of Capsids?

2001 ◽  
Vol 75 (4) ◽  
pp. 2024-2028 ◽  
Author(s):  
M. Inmaculada Barrasa ◽  
Ju-Tao Guo ◽  
Jeffrey Saputelli ◽  
William S. Mason ◽  
Christoph Seeger
Keyword(s):  
Core Protein ◽  
Sequence Motif ◽  
Rna Packaging ◽  
Viral Dna ◽  
Cdc2 Kinase ◽  
Viral Capsids ◽  
The Core ◽  
Recognition Motif ◽  
Duck Hepatitis ◽  
B Virus

ABSTRACT Hepadnaviruses are enveloped viruses, each with a DNA genome packaged in an icosahedral nucleocapsid, which is the site of viral DNA synthesis. In the presence of envelope proteins, DNA-containing nucleocapsids are assembled into virions and secreted, but in the absence of these proteins, nucleocapsids deliver viral DNA into the cell nucleus. Presumably, this step is identical to the delivery of viral DNA during the initiation of an infection. Unfortunately, the mechanisms triggering the disintegration of subviral core particles and delivery of viral DNA into the nucleus are not yet understood. We now report the identification of a sequence motif resembling a serine- or threonine-proline kinase recognition site in the core protein at a location that is required for the assembly of core polypeptides into capsids. Using duck hepatitis B virus, we demonstrated that mutations at this sequence motif can have profound consequences for RNA packaging, DNA replication, and core protein stability. Furthermore, we found a mutant with a conditional phenotype that depended on the cell type used for virus replication. Our results support the hypothesis predicting that this motif plays a role in assembly and disassembly of viral capsids.

scholarly journals Influence of a Putative Intermolecular Interaction between Core and the Pre-S1 Domain of the Large Envelope Protein on Hepatitis B Virus Secretion

2002 ◽  
Vol 76 (13) ◽  
pp. 6510-6517 ◽  
Author(s):  
Sophie Le Pogam ◽  
Chiaho Shih
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Wild Type ◽  
The Core ◽  
Virion Release ◽  
Naturally Occurring ◽  
B Virus ◽  
Kinetics Of ◽  
Viral Reverse Transcription

ABSTRACT Virion release of hepatitis B virus (HBV) from hepatocytes is a tightly regulated event. It is a dogma that only the mature HBV genome is preferentially allowed to export from the intracellular compartment (J. Summers and W. S. Mason, Cell 29:403-415, 1982). Recently, an “immature secretion” phenotype of a highly frequent naturally occurring HBV variant containing a leucine residue at amino acid 97 of the core protein was identified. Unlike wild-type HBV, this variant secretes almost equal amounts of mature and immature genomes. This phenomenon is not caused by any instability of core particles or by any deficiency in viral reverse transcription (T. T. Yuan, P. C. Tai, and C. Shih, J. Virol. 73:10122-10128, 1999). In this study, our kinetic analysis of virion secretion of the mutant F97L (phenylalanine to leucine) indicates that the secretion of its immature genome does not occur earlier than that of its mature genome. In addition, the secretion kinetics of the mature genomes are comparable between the wild-type HBV and the mutant F97L. Therefore, the immature secretion phenomenon of mutant F97L is not caused by premature secretion or more efficient secretion. Previously, we hypothesized that the immature secretion phenotype is probably caused by the aberrant interaction between its mutant core and wild-type envelope proteins. Here, we further demonstrated that a pre-S1 envelope mutation at position 119, changing an alanine (A) to a phenylalanine (F), can offset the immature secretion phenotype of the mutant I97L (isoleucine to leucine) and successfully restore the wild-type-like selective export of the mature genome of the double mutant pre-S1-A119F/core-I97L.

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