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1.
Biomed Res Int ; 2022: 8078259, 2022.
Article in English | MEDLINE | ID: covidwho-1822112

ABSTRACT

Coronaviruses are a family of viruses that infect mammals and birds. Coronaviruses cause infections of the respiratory system in humans, which can be minor or fatal. A comparative transcriptomic analysis has been performed to establish essential profiles of the gene expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) linked to cystic fibrosis (CF). Transcriptomic studies have been carried out in relation to SARS-CoV-2 since a number of people have been diagnosed with CF. The recognition of differentially expressed genes demonstrated 8 concordant genes shared between the SARS-CoV-2 and CF. Extensive gene ontology analysis and the discovery of pathway enrichment demonstrated SARS-CoV-2 response to CF. The gene ontological terms and pathway enrichment mechanisms derived from this research may affect the production of successful drugs, especially for the people with the following disorder. Identification of TF-miRNA association network reveals the interconnection between TF genes and miRNAs, which may be effective to reveal the other influenced disease that occurs for SARS-CoV-2 to CF. The enrichment of pathways reveals SARS-CoV-2-associated CF mostly engaged with the type of innate immune system, Toll-like receptor signaling pathway, pantothenate and CoA biosynthesis, allograft rejection, graft-versus-host disease, intestinal immune network for IgA production, mineral absorption, autoimmune thyroid disease, legionellosis, viral myocarditis, inflammatory bowel disease (IBD), etc. The drug compound identification demonstrates that the drug targets of IMIQUIMOD and raloxifene are the most significant with the significant hub DEGs.


Subject(s)
COVID-19 , Cystic Fibrosis , COVID-19/genetics , COVID-19/physiopathology , Cystic Fibrosis/genetics , Cystic Fibrosis/physiopathology , Gene Expression Profiling , Gene Ontology , Humans , MicroRNAs/genetics , SARS-CoV-2 , Transcription Factors/genetics
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332610

ABSTRACT

In this paper, we present a framework that automatically labels Latent Dirichlet Allocation (LDA) generated topics using sentiment and aspect terms from COVID-19 tweets to help the end-users by minimizing the cognitive overhead of identifying key topics labels. Social media platforms especially Twitter are considered as one of the most influential sources of information for providing public opinion related to a critical situation like the COVID-19 pandemic. LDA is a popular topic modelling algorithm that extracts hidden themes of documents without assigning a specific label. Thus automatic labelling of LDA-generated topics from COVID-19 tweets is a great challenge instead of following the manual labelling approach to get an overview of wider public opinion. To overcome this problem, in this paper, we propose a framework named \texttt{SATLabel} that effectively identifies significant topic labels using \textit{top unigrams features of sentiment terms and aspect terms clusters from LDA generated topics} of COVID-19 related tweets to uncover various issues related to the COVID-19 pandemic. The experimental results show that our methodology is more effective, simpler, and traces better topic labels compare to the manual topic labelling approach.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321162

ABSTRACT

This paper formulates the problem of dynamically identifying key topics with proper labels from COVID-19 Tweets to provide an overview of wider public opinion. Nowadays, social media is one of the best ways to connect people through Internet technology, which is also considered an essential part of our daily lives. In late December 2019, an outbreak of the novel coronavirus, COVID-19 was reported, and the World Health Organization declared an emergency due to its rapid spread all over the world. The COVID-19 epidemic has affected the use of social media by many people across the globe. Twitter is one of the most influential social media services, which has seen a dramatic increase in its use from the epidemic. Thus dynamic extraction of specific topics with labels from tweets of COVID-19 is a challenging issue for highlighting conversation instead of manual topic labeling approach. In this paper, we propose a framework that automatically identifies the key topics with labels from the tweets using the top Unigram feature of aspect terms cluster from Latent Dirichlet Allocation (LDA) generated topics. Our experiment result shows that this dynamic topic identification and labeling approach is effective having the accuracy of 85.48\% with respect to the manual static approach.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305090

ABSTRACT

Background: Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus is a significant global challenge. Many individuals who become infected have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative about individual risk of severe illness and mortality. Accurately determining how comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. Methods: To assess the interaction of patient comorbidities with COVID-19 severity and mortality we performed a meta-analysis of the published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Results: Our meta-analysis identified chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictor of mortality, in terms of symptom-comorbidity combinations, it was observed that Pneumonia-Hypertension, Pneumonia-Diabetes and Acute Respiratory Distress Syndrome (ARDS)-Hypertension showed the most significant effects on COVID-19 mortality. Conclusions: These results highlight patient cohorts most at risk of COVID-19 related severe morbidity and mortality which have implications for prioritization of hospital resources.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305089

ABSTRACT

Introduction: For COVID-19 patients accurate prediction of disease severity and mortality risk would greatly improve care delivery and resource allocation. There are many patient-related factors, such as pre-existing comorbidities that affect disease severity. Since rapid automated profiling of peripheral blood samples is widely available, we investigated how such data from the peripheral blood of COVID-19 patients might be used to predict clinical outcomes. Methods: We thus investigated such clinical datasets from COVID-19 patients with known outcomes by combining statistical comparison and correlation methods with machine learning algorithms;the latter included decision tree, random forest, variants of gradient boosting machine, support vector machine, K-nearest neighbour and deep learning methods. Results: Our work revealed several clinical parameters measurable in blood samples, which discriminated between healthy people and COVID-19 positive patients and showed predictive value for later severity of COVID-19 symptoms. We thus developed a number of analytic methods that showed accuracy and precision for disease severity and mortality outcome predictions that were above 90%. Conclusions: In sum, we developed methodologies to analyse patient routine clinical data which enables more accurate prediction of COVID-19 patient outcomes. This type of approaches could, by employing standard hospital laboratory analyses of patient blood, be utilised to identify, COVID-19 patients at high risk of mortality and so enable their treatment to be optimised.

6.
Inform Med Unlocked ; 28: 100840, 2022.
Article in English | MEDLINE | ID: covidwho-1587499

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in the development of a highly contagious respiratory ailment known as new coronavirus disease (COVID-19). Despite the fact that the prevalence of COVID-19 continues to rise, it is still unclear how people become infected with SARS-CoV-2 and how patients with COVID-19 become so unwell. Detecting biomarkers for COVID-19 using peripheral blood mononuclear cells (PBMCs) may aid in drug development and treatment. This research aimed to find blood cell transcripts that represent levels of gene expression associated with COVID-19 progression. Through the development of a bioinformatics pipeline, two RNA-Seq transcriptomic datasets and one microarray dataset were studied and discovered 102 significant differentially expressed genes (DEGs) that were shared by three datasets derived from PBMCs. To identify the roles of these DEGs, we discovered disease-gene association networks and signaling pathways, as well as we performed gene ontology (GO) studies and identified hub protein. Identified significant gene ontology and molecular pathways improved our understanding of the pathophysiology of COVID-19, and our identified blood-based hub proteins TPX2, DLGAP5, NCAPG, CCNB1, KIF11, HJURP, AURKB, BUB1B, TTK, and TOP2A could be used for the development of therapeutic intervention. In COVID-19 subjects, we discovered effective putative connections between pathological processes in the transcripts blood cells, suggesting that blood cells could be used to diagnose and monitor the disease's initiation and progression as well as developing drug therapeutics.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295140

ABSTRACT

The recent pandemic caused by the novel coronavirus SARS-CoV-2 has impacted global health by increasing mortality and unexpected infection rate. Extensive clinical research is undergoing to repurposing the old drug against this virus. So, this is an emerging need to develop therapy against the virus. Plant-derived natural products have proven to be potent therapeutics for several infections and diseases. Centella asiatica , is a native plant of the Indian subcontinent, has been vastly using as folk medicine against diseases including infectious diseases. So, using bioinformatics approach we identified and checked the phytochemicals of the plant as inhibitors against the main protease (Mpro), the key regulatory enzyme of the SARS-CoV-2 lifecycle. Computer-aided drug designing methods were performed to reveal the best nine drug-like phytochemicals those theoretically have the higher binding affinity of inhibiting Mpro. This outcome may direct to the development of potent therapeutics against the SARS-CoV-2 and demands experimental validation.

8.
Inform Med Unlocked ; 27: 100781, 2021.
Article in English | MEDLINE | ID: covidwho-1505531

ABSTRACT

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 has posed an enigmatic challenge to global public health security. Since last year, the mutagenic quality of this virus is causing changes to its genetic material. To prevent those situations, the FDA approved some emergency vaccines but there is no assurance that these will function properly in the complex human body system. In point of view, a short but efficient effort has made in this study to develop an immune epitope-based therapy for the rapid exploitation of SARS-CoV-2 by applying in silico structural biology and advancing immune information strategies. The antigenic epitopes were screened from the Surface, Membrane, Envelope proteins of SARS-CoV-2 and passed through several immunological filters to determine the best possible one. According to this, 7CD4+, 10CD8+ and 5 B-cell epitopes were found to be prominent, antigenic, immunogenic, and most importantly, highly conserved among 128 Bangladeshi and 110 other infected countries SARS-CoV-2 variants. After that, the selected epitopes and adjuvant were linked to finalize the multi-epitope vaccine by appropriate linkers. The immune simulation disclosed that the engineered vaccine could activate both humoral and innate immune responses. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLRs). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, MD simulation was performed within the highest binding affinity complex to observe the stability. Codon optimization and other physicochemical properties revealed that the vaccine would be suitable for a higher expression at cloning level. So, monitoring the overall in silico assessment, we anticipated that our engineered vaccine would be a plausible prevention against COVID-19.

9.
Comput Biol Med ; 139: 105014, 2021 12.
Article in English | MEDLINE | ID: covidwho-1499751

ABSTRACT

Coronavirus disease-19 (COVID-19) is a severe respiratory viral disease first reported in late 2019 that has spread worldwide. Although some wealthy countries have made significant progress in detecting and containing this disease, most underdeveloped countries are still struggling to identify COVID-19 cases in large populations. With the rising number of COVID-19 cases, there are often insufficient COVID-19 diagnostic kits and related resources in such countries. However, other basic diagnostic resources often do exist, which motivated us to develop Deep Learning models to assist clinicians and radiologists to provide prompt diagnostic support to the patients. In this study, we have developed a deep learning-based COVID-19 case detection model trained with a dataset consisting of chest CT scans and X-ray images. A modified ResNet50V2 architecture was employed as deep learning architecture in the proposed model. The dataset utilized to train the model was collected from various publicly available sources and included four class labels: confirmed COVID-19, normal controls and confirmed viral and bacterial pneumonia cases. The aggregated dataset was preprocessed through a sharpening filter before feeding the dataset into the proposed model. This model attained an accuracy of 96.452% for four-class cases (COVID-19/Normal/Bacterial pneumonia/Viral pneumonia), 97.242% for three-class cases (COVID-19/Normal/Bacterial pneumonia) and 98.954% for two-class cases (COVID-19/Viral pneumonia) using chest X-ray images. The model acquired a comprehensive accuracy of 99.012% for three-class cases (COVID-19/Normal/Community-acquired pneumonia) and 99.99% for two-class cases (Normal/COVID-19) using CT-scan images of the chest. This high accuracy presents a new and potentially important resource to enable radiologists to identify and rapidly diagnose COVID-19 cases with only basic but widely available equipment.


Subject(s)
COVID-19 , Deep Learning , Pneumonia, Viral , Algorithms , Humans , SARS-CoV-2 , Tomography, X-Ray Computed , X-Rays
10.
Comput Biol Med ; 138: 104891, 2021 11.
Article in English | MEDLINE | ID: covidwho-1439957

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the infection of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the novel coronavirus. In most countries, the containment of this virus spread is not controlled, which is driving the pandemic towards a more difficult phase. In this study, we investigated the impact of the Bacille Calmette Guerin (BCG) vaccination on the severity and mortality of COVID-19 by performing transcriptomic analyses of SARS-CoV-2 infected and BCG vaccinated samples in peripheral blood mononuclear cells (PBMC). A set of common differentially expressed genes (DEGs) were identified and seeded into their functional enrichment analyses via Gene Ontology (GO)-based functional terms and pre-annotated molecular pathways databases, and their Protein-Protein Interaction (PPI) network analysis. We further analysed the regulatory elements, possible comorbidities and putative drug candidates for COVID-19 patients who have not been BCG-vaccinated. Differential expression analyses of both BCG-vaccinated and COVID-19 infected samples identified 62 shared DEGs indicating their discordant expression pattern in their respected conditions compared to control. Next, PPI analysis of those DEGs revealed 10 hub genes, namely ITGB2, CXCL8, CXCL1, CCR2, IFNG, CCL4, PTGS2, ADORA3, TLR5 and CD33. Functional enrichment analyses found significantly enriched pathways/GO terms including cytokine activities, lysosome, IL-17 signalling pathway, TNF-signalling pathways. Moreover, a set of identified TFs, miRNAs and potential drug molecules were further investigated to assess their biological involvements in COVID-19 and their therapeutic possibilities. Findings showed significant genetic interactions between BCG vaccination and SARS-CoV-2 infection, suggesting an interesting prospect of the BCG vaccine in relation to the COVID-19 pandemic. We hope it may potentially trigger further research on this critical phenomenon to combat COVID-19 spread.


Subject(s)
BCG Vaccine , COVID-19 , Humans , Leukocytes, Mononuclear , Pandemics , SARS-CoV-2 , Vaccination
11.
Comput Biol Med ; 138: 104859, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433102

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) still tends to propagate and increase the occurrence of COVID-19 across the globe. The clinical and epidemiological analyses indicate the link between COVID-19 and Neurological Diseases (NDs) that drive the progression and severity of NDs. Elucidating why some patients with COVID-19 influence the progression of NDs and patients with NDs who are diagnosed with COVID-19 are becoming increasingly sick, although others are not is unclear. In this research, we investigated how COVID-19 and ND interact and the impact of COVID-19 on the severity of NDs by performing transcriptomic analyses of COVID-19 and NDs samples by developing the pipeline of bioinformatics and network-based approaches. The transcriptomic study identified the contributing genes which are then filtered with cell signaling pathway, gene ontology, protein-protein interactions, transcription factor, and microRNA analysis. Identifying hub-proteins using protein-protein interactions leads to the identification of a therapeutic strategy. Additionally, the incorporation of comorbidity interactions score enhances the identification beyond simply detecting novel biological mechanisms involved in the pathophysiology of COVID-19 and its NDs comorbidities. By computing the semantic similarity between COVID-19 and each of the ND, we have found gene-based maximum semantic score between COVID-19 and Parkinson's disease, the minimum semantic score between COVID-19 and Multiple sclerosis. Similarly, we have found gene ontology-based maximum semantic score between COVID-19 and Huntington disease, minimum semantic score between COVID-19 and Epilepsy disease. Finally, we validated our findings using gold-standard databases and literature searches to determine which genes and pathways had previously been associated with COVID-19 and NDs.


Subject(s)
COVID-19 , MicroRNAs , Nervous System Diseases , Computational Biology , Humans , Nervous System Diseases/genetics , SARS-CoV-2
12.
J Pers Med ; 11(9)2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1417165

ABSTRACT

Human civilization is experiencing a critical situation that presents itself for a new coronavirus disease 2019 (COVID-19). This virus emerged in late December 2019 in Wuhan city, Hubei, China. The grim fact of COVID-19 is, it is highly contagious in nature, therefore, spreads rapidly all over the world and causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Responding to the severity of COVID-19 research community directs the attention to the analysis of COVID-19, to diminish its antagonistic impact towards society. Numerous studies claim that the subcontinent, i.e., Bangladesh, India, and Pakistan, could remain in the worst affected region by the COVID-19. In order to prevent the spread of COVID-19, it is important to predict the trend of COVID-19 beforehand the planning of effective control strategies. Fundamentally, the idea is to dependably estimate the reproduction number to judge the spread rate of COVID-19 in a particular region. Consequently, this paper uses publicly available epidemiological data of Bangladesh, India, and Pakistan to estimate the reproduction numbers. More specifically, we use various models (for example, susceptible infection recovery (SIR), exponential growth (EG), sequential Bayesian (SB), maximum likelihood (ML) and time dependent (TD)) to estimate the reproduction numbers and observe the model fitness in the corresponding data set. Experimental results show that the reproduction numbers produced by these models are greater than 1.2 (approximately) indicates that COVID-19 is gradually spreading in the subcontinent.

13.
Inform Med Unlocked ; 26: 100709, 2021.
Article in English | MEDLINE | ID: covidwho-1373080

ABSTRACT

The novel COVID-19 is a global pandemic disease overgrowing worldwide. Computer-aided screening tools with greater sensitivity are imperative for disease diagnosis and prognosis as early as possible. It also can be a helpful tool in triage for testing and clinical supervision of COVID-19 patients. However, designing such an automated tool from non-invasive radiographic images is challenging as many manually annotated datasets are not publicly available yet, which is the essential core requirement of supervised learning schemes. This article proposes a 3D Convolutional Neural Network (CNN)-based classification approach considering both the inter-and intra-slice spatial voxel information. The proposed system is trained end-to-end on the 3D patches from the whole volumetric Computed Tomography (CT) images to enlarge the number of training samples, performing the ablation studies on patch size determination. We integrate progressive resizing, segmentation, augmentations, and class-rebalancing into our 3D network. The segmentation is a critical prerequisite step for COVID-19 diagnosis enabling the classifier to learn prominent lung features while excluding the outer lung regions of the CT scans. We evaluate all the extensive experiments on a publicly available dataset named MosMed, having binary- and multi-class chest CT image partitions. Our experimental results are very encouraging, yielding areas under the Receiver Operating Characteristics (ROC) curve of 0 . 914 ± 0 . 049 and 0 . 893 ± 0 . 035 for the binary- and multi-class tasks, respectively, applying 5-fold cross-validations. Our method's promising results delegate it as a favorable aiding tool for clinical practitioners and radiologists to assess COVID-19.

14.
Brief Bioinform ; 22(2): 1451-1465, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1352119

ABSTRACT

This study aimed to identify significant gene expression profiles of the human lung epithelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We performed a comparative genomic analysis to show genomic observations between SARS-CoV and SARS-CoV-2. A phylogenetic tree has been carried for genomic analysis that confirmed the genomic variance between SARS-CoV and SARS-CoV-2. Transcriptomic analyses have been performed for SARS-CoV-2 infection responses and pulmonary arterial hypertension (PAH) patients' lungs as a number of patients have been identified who faced PAH after being diagnosed with coronavirus disease 2019 (COVID-19). Gene expression profiling showed significant expression levels for SARS-CoV-2 infection responses to human lung epithelial cells and PAH lungs as well. Differentially expressed genes identification and integration showed concordant genes (SAA2, S100A9, S100A8, SAA1, S100A12 and EDN1) for both SARS-CoV-2 and PAH samples, including S100A9 and S100A8 genes that showed significant interaction in the protein-protein interactions network. Extensive analyses of gene ontology and signaling pathways identification provided evidence of inflammatory responses regarding SARS-CoV-2 infections. The altered signaling and ontology pathways that have emerged from this research may influence the development of effective drugs, especially for the people with preexisting conditions. Identification of regulatory biomolecules revealed the presence of active promoter gene of SARS-CoV-2 in Transferrin-micro Ribonucleic acid (TF-miRNA) co-regulatory network. Predictive drug analyses provided concordant drug compounds that are associated with SARS-CoV-2 infection responses and PAH lung samples, and these compounds showed significant immune response against the RNA viruses like SARS-CoV-2, which is beneficial in therapeutic development in the COVID-19 pandemic.


Subject(s)
COVID-19/complications , Hypertension, Pulmonary/complications , SARS-CoV-2/isolation & purification , Algorithms , Biomarkers/metabolism , COVID-19/metabolism , COVID-19/virology , Gene Ontology , Humans , Hypertension, Pulmonary/metabolism , Information Storage and Retrieval , MicroRNAs/metabolism , Phylogeny , Protein Interaction Maps , Transcription Factors/metabolism
15.
Brief Bioinform ; 22(2): 1415-1429, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1352118

ABSTRACT

With the increasing number of immunoinflammatory complexities, cancer patients have a higher risk of serious disease outcomes and mortality with SARS-CoV-2 infection which is still not clear. In this study, we aimed to identify infectome, diseasome and comorbidities between COVID-19 and cancer via comprehensive bioinformatics analysis to identify the synergistic severity of the cancer patient for SARS-CoV-2 infection. We utilized transcriptomic datasets of SARS-CoV-2 and different cancers from Gene Expression Omnibus and Array Express Database to develop a bioinformatics pipeline and software tools to analyze a large set of transcriptomic data and identify the pathobiological relationships between the disease conditions. Our bioinformatics approach revealed commonly dysregulated genes (MARCO, VCAN, ACTB, LGALS1, HMOX1, TIMP1, OAS2, GAPDH, MSH3, FN1, NPC2, JUND, CHI3L1, GPNMB, SYTL2, CASP1, S100A8, MYO10, IGFBP3, APCDD1, COL6A3, FABP5, PRDX3, CLEC1B, DDIT4, CXCL10 and CXCL8), common gene ontology (GO), molecular pathways between SARS-CoV-2 infections and cancers. This work also shows the synergistic complexities of SARS-CoV-2 infections for cancer patients through the gene set enrichment and semantic similarity. These results highlighted the immune systems, cell activation and cytokine production GO pathways that were observed in SARS-CoV-2 infections as well as breast, lungs, colon, kidney and thyroid cancers. This work also revealed ribosome biogenesis, wnt signaling pathway, ribosome, chemokine and cytokine pathways that are commonly deregulated in cancers and COVID-19. Thus, our bioinformatics approach and tools revealed interconnections in terms of significant genes, GO, pathways between SARS-CoV-2 infections and malignant tumors.


Subject(s)
COVID-19/complications , Neoplasms/complications , COVID-19/virology , Gene Ontology , Humans , SARS-CoV-2/isolation & purification , Signal Transduction , Transcriptome
16.
Sci Rep ; 11(1): 15431, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1332853

ABSTRACT

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.


Subject(s)
Epitopes/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Vaccines/immunology , Computational Biology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Humans , Immunogenicity, Vaccine/immunology , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Models, Molecular , Molecular Docking Simulation , Phylogeny , Protein Binding , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Helper-Inducer/immunology , Vaccines/pharmacology , Vaccines, DNA , Vaccines, Subunit/immunology , Viral Vaccines/immunology
17.
Brief Bioinform ; 22(2): 1387-1401, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343660

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein-protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/complications , Computational Biology , Hypertension/complications , Systems Biology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification
18.
Brief Bioinform ; 22(2): 1324-1337, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343645

ABSTRACT

To identify key gene expression pathways altered with infection of the novel coronavirus SARS-CoV-2, we performed the largest comparative genomic and transcriptomic analysis to date. We compared the novel pandemic coronavirus SARS-CoV-2 with SARS-CoV and MERS-CoV, as well as influenza A strains H1N1, H3N2 and H5N1. Phylogenetic analysis confirms that SARS-CoV-2 is closely related to SARS-CoV at the level of the viral genome. RNAseq analyses demonstrate that human lung epithelial cell responses to SARS-CoV-2 infection are distinct. Extensive Gene Expression Omnibus literature screening and drug predictive analyses show that SARS-CoV-2 infection response pathways are closely related to those of SARS-CoV and respiratory syncytial virus infections. We validated SARS-CoV-2 infection response genes as disease-associated using Kaplan-Meier survival estimates in lung disease patient data. We also analysed COVID-19 patient peripheral blood samples, which identified signalling pathway concordance between the primary lung cell and blood cell infection responses.


Subject(s)
COVID-19/immunology , Gene Expression Profiling , Lung/virology , SARS-CoV-2/genetics , COVID-19/virology , Humans , Influenza A virus/immunology , Kaplan-Meier Estimate , Lung/immunology , Reproducibility of Results
19.
Brief Bioinform ; 22(2): 1254-1266, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343630

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the cause of coronavirus disease (COVID-19) that causes a major threat to humanity. As the spread of the virus is probably getting out of control on every day, the epidemic is now crossing the most dreadful phase. Idiopathic pulmonary fibrosis (IPF) is a risk factor for COVID-19 as patients with long-term lung injuries are more likely to suffer in the severity of the infection. Transcriptomic analyses of SARS-CoV-2 infection and IPF patients in lung epithelium cell datasets were selected to identify the synergistic effect of SARS-CoV-2 to IPF patients. Common genes were identified to find shared pathways and drug targets for IPF patients with COVID-19 infections. Using several enterprising Bioinformatics tools, protein-protein interactions (PPIs) network was designed. Hub genes and essential modules were detected based on the PPIs network. TF-genes and miRNA interaction with common differentially expressed genes and the activity of TFs are also identified. Functional analysis was performed using gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway and found some shared associations that may cause the increased mortality of IPF patients for the SARS-CoV-2 infections. Drug molecules for the IPF were also suggested for the SARS-CoV-2 infections.


Subject(s)
COVID-19/complications , Idiopathic Pulmonary Fibrosis/complications , SARS-CoV-2/genetics , COVID-19/genetics , COVID-19/virology , Datasets as Topic , Epithelial Cells/virology , Gene Ontology , Genes, Viral , Humans , Lung/cytology , Lung/virology , Transcriptome
20.
Brief Bioinform ; 22(2): 1175-1196, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343624

ABSTRACT

The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA-DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein-chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein-chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic.


Subject(s)
COVID-19/virology , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Case-Control Studies , Comorbidity , Genome, Viral , Humans , MicroRNAs/metabolism , SARS Virus/genetics , Transcription Factors/metabolism
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