scholarly journals MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

2021 ◽  
Vol 22 (24) ◽  
pp. 13192
Author(s):  
Rosalia Battaglia ◽  
Ruben Alonzo ◽  
Chiara Pennisi ◽  
Angela Caponnetto ◽  
Carmen Ferrara ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
In Silico Analysis ◽  
Cell Physiology ◽  
Virus Life Cycle ◽  
Source Of Information ◽  
Bioinformatic Approach ◽  
Silico Analysis

In the last few years, microRNA-mediated regulation has been shown to be important in viral infections. In fact, viral microRNAs can alter cell physiology and act on the immune system; moreover, cellular microRNAs can regulate the virus cycle, influencing positively or negatively viral replication. Accordingly, microRNAs can represent diagnostic and prognostic biomarkers of infectious processes and a promising approach for designing targeted therapies. In the past 18 months, the COVID-19 infection from SARS-CoV-2 has engaged many researchers in the search for diagnostic and prognostic markers and the development of therapies. Although some research suggests that the SARS-CoV-2 genome can produce microRNAs and that host microRNAs may be involved in the cellular response to the virus, to date, not enough evidence has been provided. In this paper, using a focused bioinformatic approach exploring the SARS-CoV-2 genome, we propose that SARS-CoV-2 is able to produce microRNAs sharing a strong sequence homology with the human ones and also that human microRNAs may target viral RNA regulating the virus life cycle inside human cells. Interestingly, all viral miRNA sequences and some human miRNA target sites are conserved in more recent SARS-CoV-2 variants of concern (VOCs). Even if experimental evidence will be needed, in silico analysis represents a valuable source of information useful to understand the sophisticated molecular mechanisms of disease and to sustain biomedical applications.

scholarly journals Inhibitory Effect of Phytochemicals from Azadirachta indica A Juss. and Tinospora cordifolia (Thunb.) Miers against SARS-CoV-2 M pro and Spike Protease- An In Silico Analysis

2020 ◽  
Author(s):  
RAMÀKRISHNAMACHARYA CH ◽  
VANITHA MURALIKUMAR ◽  
CHANDRASEKAR SESHACHALAM
Keyword(s):  
Medicinal Plants ◽  
Azadirachta Indica ◽  
In Silico ◽  
Viral Infections ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Tinospora Cordifolia ◽  
Reference Drug ◽  
In Silico Study ◽  
Silico Analysis

COVID 19 caused by SARS-CoV-2 is spreading worldwide and affected 10 million people with a mortality rate between 0.5 % to 5%. Medicinal plants from China, Morocco, Algeria, Africa and India were tested for antiviral efficacy in SARS-CoV-2. Ayurveda Medicine described many medicinal plants. The Nimba ( Azadirachta indica A. Juss) is used in fever, bacterial and viral infections, and Amrita ( Tinospora cordifolia (Thunb.) Miers) is used as antiviral, antipyretic, and anti-inflammatory purposes. The combination of both these plants is called Nimbamritam, and it is widely used in pyrexia, dermatitis, viral infections, etc. Spike protease (PDB ID 6VXX) and M pro (PDB ID 6LU) were retrieved from RCSB and 16 ligands from A. indica and 6 ligands from T. cordifolia were obtained from IMPPAT and PubChem. AutoDock Vina embedded PyRx was used for docking. Remdesivir was taken as a reference drug. In silico study of Cordifolide A of T cordifolia showed the highest scores with -8.2 Kcal/mol and -10.3Kcal/mol with M pro protease and Spike protease respectively. Cordifolide A had 4 H bonds and Kaempferol had 7 non-conventional bonds, including van der Waal with M pro (6LU7) protease. The interactions with 6VXX had 5 H bonds in each ligand Cordifolide A and Azadirachtin B. The prevention of virus entry by targeting spike protease host receptor ACE2 and restricting replication of the viral genome by targeting M pro residues were identified in our study. A. indica and T. cordifolia are promising therapeutic agents in COVID 19.

scholarly journals Depolarization-Associated CircRNA Regulate Neural Gene Expression and in Some Cases May Function as Templates for Translation

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Ebrahim Mahmoudi ◽  
Dylan Kiltschewskij ◽  
Chantel Fitzsimmons ◽  
Murray J. Cairns
Keyword(s):  
Cellular Response ◽  
Neuroblastoma Cells ◽  
In Silico Analysis ◽  
Mammalian Brain ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Altered Expression ◽  
New Class ◽  
Silico Analysis ◽  
Host Genes

Circular RNAs (circRNAs) are a relatively new class of RNA transcript with high abundance in the mammalian brain. Here, we show that circRNAs expression in differentiated neuroblastoma cells were significantly altered after depolarization with 107 upregulated and 47 downregulated circRNAs. This coincided with a global alteration in the expression of microRNA (miRNA) (n = 269) and mRNA (n = 1511) in depolarized cells, suggesting a regulatory axis of circRNA–miRNA–mRNA is involved in the cellular response to neural activity. In support of this, our in silico analysis revealed that the circular transcripts had the capacity to influence mRNA expression through interaction with common miRNAs. Loss-of-function of a highly expressed circRNA, circ-EXOC6B, resulted in altered expression of numerous mRNAs enriched in processes related to the EXOC6B function, suggesting that circRNAs may specifically regulate the genes acting in relation to their host genes. We also found that a subset of circRNAs, particularly in depolarized cells, were associated with ribosomes, suggesting they may be translated into protein. Overall, these data support a role for circRNAs in the modification of gene regulation associated with neuronal activity.

scholarly journals In vitro and in silico analysis of the effects of D2 receptor antagonist target binding kinetics on the cellular response to fluctuating dopamine concentrations

2018 ◽  
Vol 175 (21) ◽  
pp. 4121-4136 ◽  
Author(s):  
Wilhelmus E A de Witte ◽  
Joost W Versfelt ◽  
Maria Kuzikov ◽  
Solene Rolland ◽  
Victoria Georgi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
In Silico ◽  
Cellular Response ◽  
D2 Receptor ◽  
In Silico Analysis ◽  
Binding Kinetics ◽  
Target Binding ◽  
Silico Analysis

scholarly journals Cellular and Molecular Response of Macrophages THP-1 during Co-Culture with Inactive Trichophyton rubrum Conidia

2020 ◽  
Vol 6 (4) ◽  
pp. 363
Author(s):  
Gabriela Gonzalez Segura ◽  
Bruna Aline Cantelli ◽  
Kamila Peronni ◽  
Pablo Rodrigo Sanches ◽  
Tatiana Takahasi Komoto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Trichophyton Rubrum ◽  
In Silico Analysis ◽  
Diabetic Patients ◽  
Molecular Response ◽  
Cellular Defense ◽  
Invasive Infections ◽  
Nuclear Factor Kappa Beta ◽  
Silico Analysis

Trichophyton rubrum is causing an increasing number of invasive infections, especially in immunocompromised and diabetic patients. The fungal invasive infectious process is complex and has not yet been fully elucidated. Therefore, this study aimed to understand the cellular and molecular mechanisms during the interaction of macrophages and T. rubrum. For this purpose, we used a co-culture of previously germinated and heat-inactivated T. rubrum conidia placed in contact with human macrophages cell line THP-1 for 24 h. This interaction led to a higher level of release of interleukins IL-6, IL-2, nuclear factor kappa beta (NF-κB) and an increase in reactive oxygen species (ROS) production, demonstrating the cellular defense by macrophages against dead fungal elements. Cell viability assays showed that 70% of macrophages remained viable during co-culture. Human microRNA expression is involved in fungal infection and may modulate the immune response. Thus, the macrophage expression profile of microRNAs during co-culture revealed the modulation of 83 microRNAs, with repression of 33 microRNAs and induction of 50 microRNAs. These data were analyzed using bioinformatics analysis programs and the modulation of the expression of some microRNAs was validated by qRT-PCR. In silico analysis showed that the target genes of these microRNAs are related to the inflammatory response, oxidative stress, apoptosis, drug resistance, and cell proliferation.

scholarly journals Crosstalk between microRNA-122 and FOX family genes in HepG2 cells

2016 ◽  
Vol 242 (4) ◽  
pp. 436-440 ◽  
Author(s):  
Subodh Kumar ◽  
Ankita Batra ◽  
Shruthi Kanthaje ◽  
Sujata Ghosh ◽  
Anuradha Chakraborti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Interactions ◽  
In Silico ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Transcript Level ◽  
Forkhead Box ◽  
Fox Genes ◽  
Silico Analysis

MicroRNA-122 (miR-122) is liver specific and plays an important role in physiology as well as diseases including hepatocellular carcinoma (HCC). Downregulation of miR-122 in HCC modulates apoptosis. Similarly, the putative targets of miR-122, the forkhead box (FOX) family genes also play an important role in the regulation of apoptosis. Hence, an interplay between miR-122 and FOX family genes has been explored in this study. Initially, an augmentation of apoptosis was noticed in HepG2 cells after transfection with miR-122. Further, the predicted miR-122 targets, the FOX family genes ( FOXM1b, FOXP1, and FOXO4) were selected via in silico analysis based on their role in apoptosis. We checked the expression of all these genes at transcript level after the transfection of miR-122 and found that the relative expression of FOXP1 and FOXM1b was significantly downregulated (p < 0.005) and that of FOXO4 was upregulated (p < 0.005). Thus, the finding indicates deregulation of these FOX genes as a result of miR-122 augmentation might be involved in the modulation of apoptosis. Impact Statement Here, we have investigated the crosstalk between microRNA-122 (miR-122) and selective FOX family genes in HepG2 cells. miR-122 is a prominent miRNA in liver and has been reported to be downregulated in hepatocellular carcinoma (HCC). It has been speculated that diminished level of miR-122 during HCC might be one of the reasons for tumor progression. However, the exact molecular interactions are not clear yet. This study unravels one of the molecular mechanisms of miR-122 through which it might impact the tumorigenesis of HCC.

scholarly journals A Resource for the Network Representation of Cell Perturbations Caused by SARS-CoV-2 Infection

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 450
Author(s):  
Livia Perfetto ◽  
Elisa Micarelli ◽  
Marta Iannuccelli ◽  
Prisca Lo Surdo ◽  
Giulio Giuliani ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cellular Proteins ◽  
Health Concern ◽  
Cell Physiology ◽  
Signaling Proteins ◽  
Major Health ◽  
New Strategy ◽  
Extensive Information ◽  
Cellular Phenotypes ◽  
Bioinformatic Approach

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.3 million casualties worldwide and the lack of effective treatments is a major health concern. The development of targeted drugs is held back due to a limited understanding of the molecular mechanisms underlying the perturbation of cell physiology observed after viral infection. Recently, several approaches, aimed at identifying cellular proteins that may contribute to COVID-19 pathology, have been reported. Albeit valuable, this information offers limited mechanistic insight as these efforts have produced long lists of cellular proteins, the majority of which are not annotated to any cellular pathway. We have embarked in a project aimed at bridging this mechanistic gap by developing a new bioinformatic approach to estimate the functional distance between a subset of proteins and a list of pathways. A comprehensive literature search allowed us to annotate, in the SIGNOR 2.0 resource, causal information underlying the main molecular mechanisms through which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related coronaviruses affect the host–cell physiology. Next, we developed a new strategy that enabled us to link SARS-CoV-2 interacting proteins to cellular phenotypes via paths of causal relationships. Remarkably, the extensive information about inhibitors of signaling proteins annotated in SIGNOR 2.0 makes it possible to formulate new potential therapeutic strategies. The proposed approach, which is generally applicable, generated a literature-based causal network that can be used as a framework to formulate informed mechanistic hypotheses on COVID-19 etiology and pathology.

scholarly journals The Unfolded Protein Response and Autophagy on the Crossroads of Coronaviruses Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Elisa B. Prestes ◽  
Julia C. P. Bruno ◽  
Leonardo H. Travassos ◽  
Leticia A. M. Carneiro
Keyword(s):  
Viral Replication ◽  
Unfolded Protein Response ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Cellular Stress ◽  
Membrane Vesicles ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The ability to sense and adequately respond to variable environmental conditions is central for cellular and organismal homeostasis. Eukaryotic cells are equipped with highly conserved stress-response mechanisms that support cellular function when homeostasis is compromised, promoting survival. Two such mechanisms – the unfolded protein response (UPR) and autophagy – are involved in the cellular response to perturbations in the endoplasmic reticulum, in calcium homeostasis, in cellular energy or redox status. Each of them operates through conserved signaling pathways to promote cellular adaptations that include re-programming transcription of genes and translation of new proteins and degradation of cellular components. In addition to their specific functions, it is becoming increasingly clear that these pathways intersect in many ways in different contexts of cellular stress. Viral infections are a major cause of cellular stress as many cellular functions are coopted to support viral replication. Both UPR and autophagy are induced upon infection with many different viruses with varying outcomes – in some instances controlling infection while in others supporting viral replication and infection. The role of UPR and autophagy in response to coronavirus infection has been a matter of debate in the last decade. It has been suggested that CoV exploit components of autophagy machinery and UPR to generate double-membrane vesicles where it establishes its replicative niche and to control the balance between cell death and survival during infection. Even though the molecular mechanisms are not fully elucidated, it is clear that UPR and autophagy are intimately associated during CoV infections. The current SARS-CoV-2 pandemic has brought renewed interest to this topic as several drugs known to modulate autophagy – including chloroquine, niclosamide, valinomycin, and spermine – were proposed as therapeutic options. Their efficacy is still debatable, highlighting the need to better understand the molecular interactions between CoV, UPR and autophagy.

scholarly journals Malaria and Burkitt’s Lymphoma: An In Silico Analysis of Gene Expression Links between Malaria and Burkitt’s Lymphoma and Potential Anticancer Activity of Artemisinin Derivatives

2018 ◽  
Author(s):  
Inas Elsayed ◽  
Mutaz Amin ◽  
Muzamil Mahdi Abdel Hamid ◽  
Xiaosheng Wang ◽  
Mie Rizig
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
In Silico Analysis ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Artemisinin Derivatives ◽  
Silico Analysis

AbstractBackgroundBurkitt’s lymphoma (BL) is an aggressive form of B-cell non-Hodgkin lymphoma. Endemic subtype of the disease showed a remarkable statistical and epidemiological association with malaria infection. Despite the numerous studies performed to explain this association; molecular mechanisms underlie such coincidence still remain unclear. Dissecting molecular mechanisms which link Malaria infection and Burkitt’s lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives.MethodsHere we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitt’s lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitt’s lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitt’s lymphoma from Gene Expression Omnibus database, expression patterns in the two conditions were examined through clustering analysis using Self Organizing Maps, and then by significance testing of differentially expressed genes in each condition followed by Functional annotation using Gene Ontology clustering and Pathways analysis.ResultsClustering analysis identified a significant overlap between the expression patterns in endemic Burkitt’s lymphoma and Plasmodium falciparum infected cells. Four out of the 12 identified clusters contained genes with similar expression patterns in both conditions. Differential expression analysis identified 1689 genes as significantly differentially expressed in endemic Burkitt’s lymphoma and 405 in malaria. Those genes were found to be related to important Gene Ontology terms and pathways. Interestingly 65% of the identified pathways in Malaria were overlapped with those identified in endemic Burkitt’s lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives.ConclusionOur In-silico analysis showed a significant molecular convergence between endemic Burkitt’s lymphoma and malaria. A number of 43pathways which demonstrated enrichment in tumour were shared with Plasmodium falciparum infected erythrocytes. Such pathways represent potential targets for antimalarial drugs to exert therapeutic effects in such malignancy.

scholarly journals Inhibitory Effect of Phytochemicals from Azadirachta indica A Juss. and Tinospora cordifolia (Thunb.) Miers against SARS-CoV-2 Mpro and Spike Protease- An In Silico Analysis

2020 ◽  
Author(s):  
RAMAKRISHNAMACHARYA CH ◽  
VANITHA MURALIKUMAR ◽  
CHANDRASEKAR S
Keyword(s):  
Medicinal Plants ◽  
Azadirachta Indica ◽  
In Silico ◽  
Viral Infections ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Tinospora Cordifolia ◽  
Autodock Vina ◽  
Reference Drug ◽  
Silico Analysis

Abstract COVID 19 caused by SARS-CoV-2 is spreading worldwide and affected 10 million people with a mortality rate between 0.5 % to 5%. Medicinal plants from China, Morocco, Algeria, Africa and India were tested for antiviral efficacy in SARS-CoV-2. Ayurveda Medicine described many medicinal plants. The Nimba (Azadirachta indica A. Juss) is used in fever, bacterial and viral infections, and Amrita (Tinospora cordifolia (Thunb.) Miers) is used as antiviral, antipyretic, and anti-inflammatory purposes. The combination of both these plants is called Nimbamritam, and it is widely used in pyrexia, dermatitis, viral infections, etc. Spike protease (PDB ID 6VXX) and Mpro (PDB ID 6LU) were retrieved from RCSB and 16 ligands from A. indica and 6 ligands from T. cordifolia were obtained from IMPPAT and PubChem. AutoDock Vina embedded PyRx was used for docking. Remdesivir was taken as a reference drug. In silico study of Cordifolide A of T cordifolia showed the highest scores with -8.2 Kcal/mol and -10.3Kcal/mol with Mpro protease and Spike protease respectively. Cordifolide A had 4 H bonds and Kaempferol had 7 non-conventional bonds, including van der Waal with Mpro (6LU7) protease. The interactions with 6VXX had 5 H bonds in each ligand Cordifolide A and Azadirachtin B. The prevention of virus entry by targeting spike protease host receptor ACE2 and restricting replication of the viral genome by targeting Mpro residues were identified in our study. A. indica and T. cordifolia are promising therapeutic agents in COVID 19.

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