scholarly journals In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Asmae Saih ◽  
Hana Baba ◽  
Meryem Bouqdayr ◽  
Hassan Ghazal ◽  
Salsabil Hamdi ◽  
...  
Keyword(s):  
Protein Structure ◽  
High Risk ◽  
In Silico ◽  
In Silico Analysis ◽  
Host Cells ◽  
Structure Stability ◽  
Missense Variants ◽  
Cumulative Score ◽  
And Function ◽  
Silico Analysis

SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various bioinformatics tools were used including SIFT, PANTHER, PROVEAN, PolyPhen2.0, I. Mutant Suite, MUpro, SWISS-MODEL, Project HOPE, ModPred, QMEAN, ConSurf, and STRING. All twelve ACE2 nsSNPs were analyzed. Six ACE2 high-risk pathogenic nsSNPs (D427Y, R514G, R708W, R710C, R716C, and R768W) were found to be the most damaging by at least six software tools (cumulative score between 6 and 7) and exert deleterious effect on the ACE2 protein structure and likely function. Additionally, they revealed high conservation, less stability, and having a role in posttranslation modifications such a proteolytic cleavage or ADP-ribosylation. This in silico analysis provides information about functional nucleotide variants that have an impact on the ACE2 protein structure and function and therefore susceptibility to SARS-CoV-2.

scholarly journals In silico analysis of Missense Variants in Human MPL Gene Associated with Essential Thrombocythemia

2019 ◽  
Author(s):  
Sahar G. Elbager ◽  
Abier A. Makkawi ◽  
Hadeel A. Mohamed ◽  
Fauzia A. Abdelrahman ◽  
Lamia H. Osman ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
In Silico ◽  
Association Studies ◽  
In Silico Analysis ◽  
Structure And Function ◽  
Janus Kinase ◽  
Hematopoietic Stem ◽  
Missense Variants ◽  
And Function ◽  
Silico Analysis

AbstractIntroductionThe proto-oncogene (MPL) gen encodes the receptor for thrombopoietin (TPO-R), a member of hematopoietic receptor superfamily. Thrombopoietin (TPO), the primary cytokine regulating self-renewal of hematopoietic stem cells, thrombopoiesis and megakaryocytopoiesis. TPO binding to TPO-R induces activation of Janus Kinase 2 (JAK2). Activated JAK2 triggers the activation of downstream positive signaling pathways, leading to the survival, proliferation, and differentiation of hematopoietic cells. Mutations in MPL gene possibly will alter the normal regulatory mechanisms. Numerous MPL mutations have been observed in various hematopoietic cancers such as essential thrombocythemia and primary myelofibrosis and leukemias. In this study, we performed a comprehensive in silico analysis of the functional and structural impact of non-synonymous (nsSNP) that are deleterious to TPO-R structure and function.MethodologyThe data on human MPL gene was retrieved from dbSNP/NCBI. Nine prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Condel, PhD-SNP, I-Mutant, Mutpred. RaptorX and Chimera were used to analyzing the effect of nsSNPs on functions and structure of the TPO-R. STRING and KEGG database were used for TPO-R protein-protein interaction.Results and DiscussionAs per dbSNP database, the human MPL gene contained 445 missense mutations. A total 5 nsSNPs (D295G, R257C, Y252H, R537W and D128Y) were predicted to have the most damaging effects on TPO-R structure and function. STRING and KEGG revealed that MPL had strong interactions with proteins that involved in cell growth, apoptosis, signal transduction pathway, some cancers pathways such as colorectal cancer, lung cancer, pancreas cancers, and skin cancer. A literature search revealed that Y252H has contribute to the development of essential thrombocythemia.ConclusionThese in silico predictions will provide useful information in selecting the target SNPs that are likely to have functional impact on the TPO-R and moreover could act as potential targets in genetic association studies. Keywords: In Silico analyses; JAK2; Missense Variants; MPL gene; Thrombopoietin (TPO); Single nucleotide polymorphism (SNP).

scholarly journals In silico analysis of CDC73 gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

2019 ◽  
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Alaa I. Mohammed ◽  
Esraa O. Gadim ◽  
Mayada A.Mohammed ◽  
Sara H. Hamza ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Dominant ◽  
In Silico Analysis ◽  
Autosomal Dominant Disorder ◽  
Variable Expression ◽  
Back Ground ◽  
And Function ◽  
Molecular Aberrations ◽  
The Impact ◽  
Silico Analysis

AbstractBack groundhyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs on CDC73 structure and function using different bioinformatics tools.MethodComputational analysis using eight different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function of CDC73 gene that might be causing jaw tumour.ResultsFrom (733) SNPs identified in the CDC73 gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.ConclusionEleven substantial genetic/molecular aberrations in CDC73 gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.

scholarly journals Comprehensive in silico Analysis of IKBKAP gene that could potentially cause Familial dysautonomia

2018 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Enas A. Osman ◽  
Abdelrahman H. Abdelmoneiom ◽  
Dania M. Hassn ◽  
Hadeel M. Yousif ◽  
...  
Keyword(s):  
In Silico ◽  
Genetic Disorder ◽  
In Silico Analysis ◽  
Familial Dysautonomia ◽  
Structural Effect ◽  
Structure And Function ◽  
Genetic Studies ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundFamilial dysautonomia (FD) is a rare neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies. We aimed to identify the pathogenic SNPs in IKBKAP gene by computational analysis software’s, and to determine the structure, function and regulation of their respective proteins.Materials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict SNPs influence on protein structure and function.Result41 novel mutations out of 973 nsSNPs that are found be deleterious effect on the IKBKAP structure and function.ConclusionThis is the first in silico analysis in IKBKAP gene to prioritize SNPs for further genetic studies.

scholarly journals A Review on the Novel Coronavirus Disease based on In-silico Analysis of Various Drugs and Target Proteins

2020 ◽  
Vol 14 (suppl 1) ◽  
pp. 849-860
Author(s):  
Gauravi N. Trivedi ◽  
Janhavi T. Karlekar ◽  
Hiren A. Dhameliya ◽  
Hetalkumar Panchal
Keyword(s):  
In Silico ◽  
Close Contact ◽  
Genome Structure ◽  
In Silico Analysis ◽  
Bioactive Compound ◽  
Host Cells ◽  
World Health ◽  
Large Set ◽  
Genomic Rnas ◽  
Silico Analysis

Coronavirus Disease (COVID-19) is a new disease that emerged in Wuhan, China which spreads through close contact of people, often by small droplets produced during coughing or sneezing. Detail mechanism by which it spreads between people are under investigation. The World Health Organization (WHO) declared this disease as a pandemic after the severity of the disease increased. Many scientific reports gathered have suggested many drugs that could be potential candidates for the treatment. Although, clinical effectiveness has not been fully evaluated. In this review, we have aggregated the data from few research articles, official news websites and few review papers regarding its phylogenetic relation, genomic constitution, transmission, replication and in-silico analysis done by researchers for few potent drugs that are currently used to cure COVID-19. SARS-CoV-2 belongs to Betacoronavirus genus with Genome structure consists 14 Open Reading Frames (ORFs) that encode 27 proteins. Coronavirus replicates into the host cells having unique mechanisms like ribosome frame-shifting and synthesis of genomic and sub genomic RNAs. In-silico methods have the advantage that they can make fast predictions for a large set of compounds in a high-throughput mode and also make their prediction based on the structure of a compound even before it has been synthesized. In-silico softwares have been used to find or to improve a novel bioactive compound, which may exhibit a strong affinity to a particular target in the drug development process.

In silico analysis of the EPS8 gene family: genomic organization, expression profile, and protein structure

Genomics ◽  
2003 ◽  
Vol 81 (2) ◽  
pp. 234-244 ◽  
Author(s):  
Arianna Tocchetti ◽  
Stefano Confalonieri ◽  
Giorgio Scita ◽  
Pier Paolo Di Fiore ◽  
Christer Betsholtz
Keyword(s):  
Protein Structure ◽  
Gene Family ◽  
Expression Profile ◽  
In Silico ◽  
Genomic Organization ◽  
In Silico Analysis ◽  
Silico Analysis

scholarly journals Identification of HPV16 in suspected cases of cervical lesions and docking Study of its L1 protein with some natural inhibitors.

2020 ◽  
Author(s):  
Yusuf Lukman ◽  
Doro Aliyu Bala ◽  
Kabir Imam Malik ◽  
Abdulkadir Saidu ◽  
Abdulhadi Sale Kumurya ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Prevalence Rate ◽  
In Silico ◽  
In Silico Analysis ◽  
Low Grade ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
L1 Protein ◽  
Silico Analysis

Abstract Background The Human papillomavirus (HPV) causes sexually transmitted diseases. Among several types of HPV variants, HPV 16 is listed as a high-risk group, the primary cervical cancer etiologic agent, which causes life-threatening disease among women worldwide. The presence of L1, E6 and E7 encoded oncoproteins are largely responsible for virulence and pathogenicity that leads to cervical lesions. This menace is required to be curbed by designing an anti-cancerous drugs. The protein receptor-inhibitor interaction adopted using in silico analysis is very important in drug designing. It was the objective of this study to identify HPV16 isolates from suspected cases of cervical cancer at SH Sokoto and SYMH Birnin Kebbi hospitals and also to identify potent HPV16’s L1 protein inhibitor using in silico analysis of Echinacoside, curcumin and Cichoric acid against the viral protein. Methods A total of 140 cervical smear samples consisting of 21 low grade squamous intraepithelial lesion, 6 high grade lesion and 117 negative pap smears were collected. The samples were subjected for molecular detection using PCR targeting E6 and L1 genes of the virus. Positive samples were sequenced using Sanger sequencing platform. All the sequencing data were analysed using bioedit software while data generated for the molecular prevalence was statistically analyzed using Chi-square. A comprehensive HPV L1 protein homology model was designed to predict the L1 protein interaction mechanism with natural inhibitory molecules using a structural drug design approach. AutoDock Vina was used to carry out the molecular docking. Results Out of the 140 samples, 24 samples were positive for the PCR representing 16.7% molecular prevalence rate. There is statistically significant association between cyto-diagnoses and presence of HPV16 ( P ˂0.05). The highest prevalence rate of 12(50% of positive sample) was recorded among women between 30-39 years old. Docking analysis showed that the Chicoric acid components of Echinacea purpurae have strong binding affinity to the L1 protein of the HPV. Conclusion This study provides data on HPV 16 epidemiology in northern Nigeria, High-risk type 16 HPV variant was identified and also provides novel evidence for consideration on certain interacting residues, when synthesizing Anti-HPV compounds in the wet lab.

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