scholarly journals Computational Prediction of HCV RNA Polymerase Inhibitors from Alkaloid Library

2021 ◽  
Vol 11 (3) ◽  
pp. 3661-3671
Keyword(s):  
Living Organism ◽  
Computational Prediction ◽  
Vital Role ◽  
Chronic Liver ◽  
Hcv Rna ◽  
Propanoic Acid ◽  
Amino Acid Residues ◽  
Global Challenge ◽  
Docking Approach ◽  
Chronic Hcv

Hepatitis C virus (HCV) is a global challenge and the leading cause of chronic liver disease. Approximately 30% of a patient infected with chronic HCV results into liver cirrhosis. WHO reports that 3% of the world’s population has been infected with HCV, which signifies that about 170 million people are at risk of developing chronic liver diseases globally. Research has shown that HCV NS5B polymerase is one of the six non-structural proteins encoded in the approximately 9600 nucleotide genome of HCV, which plays a vital role in the replication and infection of HCV virus; therefore, it serves as a target enzyme for antiviral therapy against HCV. In this study, Alkaloids, a group of vital secondary metabolites in plants, with cyclic structures containing nitrogen in a negative oxidation state which is limitedly distributed in a living organism, were mined from an online database and screened computationally using a molecular docking approach to predict its inhibitory potential against the replication of HCV’s viral RNA. 259 Alkaloids was retrieved and docked, and it resulted that 3-(4-methoxyphenyl)-3-[[2-(4-methoxyphenyl)-1-oxoethyl]amino]propanoic acid, 14-norpseurotin A, and (+)-aplysinilin are predicted to be suitable inhibitors against NS5B through their binding pose and interactions with the amino acid residues at the binding site of NS5B. Additionally, hit compounds from the docking result were further subjected to ADME/Tox screening to predict their drug-likeness characteristics, and 3-(4-methoxyphenyl)-3-[[2-(4-methoxyphenyl)-1-oxoethyl]amino]propanoic acid stands out by showing more drug-like characteristics.

scholarly journals PredNTS: Improved and Robust Prediction of Nitrotyrosine Sites by Integrating Multiple Sequence Features

2021 ◽  
Vol 22 (5) ◽  
pp. 2704
Author(s):  
Andi Nur Nilamyani ◽  
Firda Nurul Auliah ◽  
Mohammad Ali Moni ◽  
Watshara Shoombuatong ◽  
Md Mehedi Hasan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Web Application ◽  
Computational Prediction ◽  
Vital Role ◽  
Machine Learning Algorithms ◽  
Recursive Feature Elimination ◽  
Post Translational Modification ◽  
Multiple Sequence ◽  
Sequence Features

Nitrotyrosine, which is generated by numerous reactive nitrogen species, is a type of protein post-translational modification. Identification of site-specific nitration modification on tyrosine is a prerequisite to understanding the molecular function of nitrated proteins. Thanks to the progress of machine learning, computational prediction can play a vital role before the biological experimentation. Herein, we developed a computational predictor PredNTS by integrating multiple sequence features including K-mer, composition of k-spaced amino acid pairs (CKSAAP), AAindex, and binary encoding schemes. The important features were selected by the recursive feature elimination approach using a random forest classifier. Finally, we linearly combined the successive random forest (RF) probability scores generated by the different, single encoding-employing RF models. The resultant PredNTS predictor achieved an area under a curve (AUC) of 0.910 using five-fold cross validation. It outperformed the existing predictors on a comprehensive and independent dataset. Furthermore, we investigated several machine learning algorithms to demonstrate the superiority of the employed RF algorithm. The PredNTS is a useful computational resource for the prediction of nitrotyrosine sites. The web-application with the curated datasets of the PredNTS is publicly available.

scholarly journals Hepatitis C virus infection and risk of liver-related and non-liver-related deaths: a population-based cohort study in Naples, southern Italy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pierluca Piselli ◽  
Diego Serraino ◽  
Mario Fusco ◽  
Enrico Girardi ◽  
Angelo Pirozzi ◽  
...  
Keyword(s):  
Southern Italy ◽  
Population Based ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Risk Of Death ◽  
High Prevalence ◽  
Specific Mortality ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Related Mortality

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

Demonstration and Distribution of HCV RNA Sequences by in situ Hybridization and HCV-Related Proteins by Immunohistochemistry in the Liver Tissue of Patients with Chronic HCV Infection

Pathobiology ◽  
1995 ◽  
Vol 63 (5) ◽  
pp. 239-248 ◽  
Author(s):  
Domenico Sansonno ◽  
Vito Cornacchiulo ◽  
Anna Rina Iacobelli ◽  
Pietro Gatti ◽  
Maria Di Stasi ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Liver Tissue ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Rna Sequences ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Related Proteins

scholarly journals Genetic Variants in JAK1 Gene and Susceptibility to Hepatitis C Viral Infection in Iraq

2016 ◽  
Vol 10 (1) ◽  
pp. 37-41
Author(s):  
Fatima Abood Chaloob
Keyword(s):  
Hepatitis C ◽  
Hcv Infection ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Global Challenge ◽  
Pcr Products ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Apparently Healthy

Infection with hepatitis C virus (HCV) imposes a global challenge with over 180 million cases worldwide. Only few patients spontaneously had their virus neutralized, while most patients develop chronic HCV infection. This implies a key role of genetic factors in viral clearance or persistence. The current study aimed at clarifying the effect of certain single nucleotide polymorphisms (SNPs) on individual's susceptibility to HCV infection.  A total of 60 patients with confirmed HCV infection and 35 apparently healthy individuals were enrolled in this study. Blood sample was obtained from each participant, from which DNA was extracted. The JAK1gene was amplified with conventional PCR technique using three sets of primers targeting three SNPs in this gene: rs2780895, rs4244165 and rs17127024. Restriction fragment length polymorphism (RFLP) was used for genotyping of PCR products. Each of rs2780895 and rs17127024 had two genotypes in both patients and controls, however, only the heterozygous genotype of the SNP rs2780895 (CT) significantly associated with the susceptibility to HCV. The SNP rs4244165 appeared in only with homozygous wild genotype (GG) in both patients and controls. It can be concluded that allele T of the SNP rs2780895 could be considered as a risk factor for infection with HCV

scholarly journals The Isolation and Identification of Anthocyanin-Related GSTs in Chrysanthemum

Horticulturae ◽  
2021 ◽  
Vol 7 (8) ◽  
pp. 231
Author(s):  
Yajing Li ◽  
Xiaofen Liu ◽  
Fang Li ◽  
Lili Xiang ◽  
Kunsong Chen
Keyword(s):  
Anthocyanin Biosynthesis ◽  
Vital Role ◽  
Luciferase Assay ◽  
Amino Acid Residues ◽  
Anthocyanin Accumulation ◽  
Isolation And Identification ◽  
Specific Amino Acid ◽  
Protein Sequence Alignment ◽  
Glutathione S Transferases ◽  
Transient Overexpression

Anthocyanin is the crucial pigment for the coloration of red chrysanthemum flowers, which synthesizes in the cytosol and is transported to the vacuole for stable storage. In general, glutathione S-transferases (GSTs) play a vital role in this transport. To date, there is no functional GST reported in chrysanthemums. Here, a total of 94 CmGSTs were isolated from the chrysanthemum genome, with phylogenetic analysis suggesting that 16 members of them were clustered into the Phi subgroup which was related to anthocyanin transport. Among them, the expression of CmGST1 was positively correlated with anthocyanin accumulation. Protein sequence alignment revealed that CmGST1 included anthocyanin-related GST-specific amino acid residues. Further transient overexpression experiments in tobacco leaves showed that CmGST1 could promote anthocyanin accumulation. In addition, a dual-luciferase assay demonstrated that CmGST1 could be regulated by CmMYB6, CmbHLH2 and CmMYB#7, which was reported to be related to anthocyanin biosynthesis. Taken together, we suggested that CmGST1 played a key role in anthocyanin transport and accumulation in chrysanthemums.

Correlation of biochemical markers and HCV RNA titers with fibrosis stages and grades in chronic HCV-3a patients

2014 ◽  
Vol 26 (7) ◽  
pp. 788-794 ◽  
Author(s):  
Muhammad Shahid ◽  
Muhammad Idrees ◽  
Bilal Nasir ◽  
Arsalan J. Raja ◽  
Syed M. Raza ◽  
...  
Keyword(s):  
Biochemical Markers ◽  
Hcv Rna ◽  
Chronic Hcv

scholarly journals Spontaneous Clearance of Chronic HCV: The Key Ending Left in the Dark

2019 ◽  
Vol 7 (10) ◽  
pp. 1657-1659
Author(s):  
Nikola Hristov Mumdzhiev ◽  
Daniela Valerieva Radicheva ◽  
Mariana Penkova Radicheva ◽  
Rumen Valchev Tenev ◽  
Zlatina Dimitrova Vasileva
Keyword(s):  
Hepatitis C ◽  
Hcv Rna ◽  
Spontaneous Clearance ◽  
Hepatitis C Infection ◽  
Positive Serology ◽  
Mild Disease ◽  
Spontaneous Hcv Clearance ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Special Circumstances

BACKGROUND: Hepatitis C is the second leading cause of liver cirrhosis and hepatocellular carcinoma. Although the discovery of direct-acting agents made the disease curable, HCV elimination can be achieved solely by the host’s immunologic arsenal. CASE REPORT: We report the case of a 29-year-old woman with chronic hepatitis C infection - elevated transaminases, positive serology. HCV was detectable on two occasions, and histology showed mild disease - A1F1. Upon follow up and without any treatment, the patient achieved spontaneous clearance confirmed by two consecutive undetectable HCV RNA tests. Spontaneous HCV clearance rarely occurs – 0.5% per person-year. This is sometimes accompanied by special circumstances like additional disease or medical interventions. Host factors like gender and interleukin-28B polymorphisms have been known to contribute to clearance. Viral factors like HCV RNA levels are also a factor. The characteristics of host-viral interplay – age of acquisition and fibrosis stage – cannot be overlooked. CONCLUSION: All of the abovementioned factors contribute to the complex immunological interaction between virus and host and the result, although rarely can be spontaneous clearance.

Effect of Direct Acting Anti-Viral Drugs on Insulin Resistance and sensitivity Among Egyptian Chronic HCV Infected Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tareq M Yosef ◽  
Wesam A Ibrahim ◽  
Sarah A El-Nakeep ◽  
Ahmed M ElGhandour ◽  
Soha saied attiya
Keyword(s):  
Insulin Resistance ◽  
Fasting Blood Glucose ◽  
Hcv Infection ◽  
Military Hospital ◽  
Hcv Rna ◽  
Matsuda Index ◽  
Treatment Naïve ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

Abstract Background Hepatitis C virus (HCV) infection is a worldwide infection, affecting up to 185 million people across the world. It carries a high risk for developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Aim of the Work to assess the impact of direct acting anti-viral drugs on the status of insulin resistance and sensitivity in non-diabetic chronic HCV infection patients Patients and Methods study included 100 treatment naive patients with chronic infection of HCV attending the out-patient clinic at Gastro-enterology and Hepatology Department, Ain shams University and Kobry El Kobba Military Hospital between September 2017 till June 2019. Patients were diagnosed by HCV antibodies & HCV RNA by PCR. Results The fasting blood glucose, seum insulin and HbA1c were significantly decreased between the baseline and after SVR12. The 2Hrs PP was significantly increased between the baseline and after SVR12. The HOMA-IR showed significant decrease between the baseline and SVR12. The QUICKI and Matsuda Index showed significant increase at SVR12. Conclusion HOMA-IR, QUICKI and Matsuda index showed significant improvement between the baseline and after SVR12.

Ledipasvir/Sofosbuvir in Adolescents With Chronic Hepatitis C Genotype 4 With and Without Hematological Disorders: Virological Efficacy and Impact on Liver Stiffness

2020 ◽  
Author(s):  
Nahed A Makhlouf ◽  
Mohamed O Abdelmalek ◽  
Mohamed Eltaher Ibrahim ◽  
Nagla H Abu-Faddan ◽  
Abeer E Kheila ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Stiffness ◽  
Hcv Rna ◽  
Genotype 4 ◽  
Hematological Disorders ◽  
Apri Score ◽  
Treatment Naïve ◽  
Patient Groups ◽  
Group 2 ◽  
Chronic Hcv

Abstract Background Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness. Methods Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase–platelet ratio index (APRI) score were estimated at baseline and at SVR12. Results SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P < .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects. Conclusions Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.

scholarly journals Hepatitis C elimination in the Netherlands (CELINE): study protocol for nationwide retrieval of lost to follow-up patients with chronic hepatitis C

2020 ◽  
Vol 7 (1) ◽  
pp. e000396 ◽  
Author(s):  
Cas J Isfordink ◽  
Sylvia M Brakenhoff ◽  
Marleen van Dijk ◽  
Marc van der Valk ◽  
Rob J de Knegt ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
The Netherlands ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Ethical Approval ◽  
Hcv Transmission ◽  
Chronic Hcv ◽  
Lost To Follow Up

BackgroundThe Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval.MethodsLaboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who are eligible for retrieval. These patients will be invited for outpatient clinic care. The primary outcome of the study is the total number of LTFU patients who have been successfully linked to care.DiscussionHepatitis C ELimination In the NEtherlands (CELINE) is within the remit of WHO elimination targets and the Dutch National Hepatitis Plan. The methodology of CELINE is based on previously conducted regional retrieval projects and is designed to overcome some of their limitations. After ethical approval was obtained in 2018, the first centre initiated retrieval in 2018 and the project is expected to finish in 2021.Trial registration numberNCT04208035.

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