scholarly journals Potential role of cellular miRNAs in coronavirus-host interplay

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9994 ◽  
Author(s):  
Stepan Nersisyan ◽  
Narek Engibaryan ◽  
Aleksandra Gorbonos ◽  
Ksenia Kirdey ◽  
Alexey Makhonin ◽  
...  
Keyword(s):  
Computational Prediction ◽  
Bioinformatic Analysis ◽  
Sequencing Data ◽  
Human Coronavirus ◽  
Cellular Mirnas ◽  
Mirna Sequencing ◽  
Direct Binding ◽  
Human Coronaviruses ◽  
Mouse Lungs

Host miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses through several possible mechanisms including direct binding of viral RNA. Identification of human miRNAs involved in coronavirus-host interplay becomes important due to the ongoing COVID-19 pandemic. In this article we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. As a result, we identified six miRNAs (miR-21-3p, miR-195-5p, miR-16-5p, miR-3065-5p, miR-424-5p and miR-421) with high binding probability across all analyzed viruses. Further bioinformatic analysis of binding sites revealed high conservativity of miRNA binding regions within RNAs of human coronaviruses and their strains. In order to discover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV.

scholarly journals The potential role of miR-21-3p in coronavirus-host interplay

2020 ◽  
Author(s):  
Stepan Nersisyan ◽  
Narek Engibaryan ◽  
Aleksandra Gorbonos ◽  
Ksenia Kirdey ◽  
Alexey Makhonin ◽  
...  
Keyword(s):  
Potential Role ◽  
Computational Prediction ◽  
Bioinformatic Analysis ◽  
Sequencing Data ◽  
Human Coronavirus ◽  
Mirna Sequencing ◽  
Direct Binding ◽  
Human Coronaviruses ◽  
Mouse Lungs

ABSTRACTHost miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses by several possible mechanisms including direct binding the viral RNA. Identification of human miRNAs involved in coronavirus-host interplay is becoming important due to the ongoing COVID-19 pandemic. In this work we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. In order to uncover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV. Further bioinformatic analysis of binding sites revealed high conservativity of miR-21-3p binding regions within RNAs of human coronaviruses and their strains.

The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 (Preprint)

2020 ◽  
Author(s):  
Alan T Evangelista
Keyword(s):  
Hospital Admissions ◽  
Disease Incidence ◽  
Influenza Viruses ◽  
Seasonal Effects ◽  
Human Coronavirus ◽  
Enveloped Virus ◽  
Multiplex Pcr Assay ◽  
Contact Transmission ◽  
Human Coronaviruses

UNSTRUCTURED The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern. INTERNATIONAL REGISTERED REPORT RR2-doi.org/10.1101/2020.05.15.20103416

scholarly journals The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2

2020 ◽  
Author(s):  
Alan T Evangelista
Keyword(s):  
Hospital Admissions ◽  
Disease Incidence ◽  
Influenza Viruses ◽  
Seasonal Effects ◽  
Human Coronavirus ◽  
Enveloped Virus ◽  
Multiplex Pcr Assay ◽  
Contact Transmission ◽  
Human Coronaviruses

The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.

scholarly journals A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV Genome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Md Mahmudul Hasan ◽  
Rozina Akter ◽  
Md. Shahin Ullah ◽  
Md. Jaynul Abedin ◽  
G. M. Ahsan Ullah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Middle East ◽  
Viral Replication ◽  
Viral Gene Expression ◽  
Computational Approach ◽  
Viral Gene ◽  
Fatality Rate ◽  
Human Coronavirus ◽  
Cellular Mirnas

The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.

scholarly journals Role of SNPs in the biogenesis of mature miRNAs

2020 ◽  
Author(s):  
Ying Wang ◽  
Jidong Ru ◽  
Meng Xianglian
Keyword(s):  
Molecular Mechanisms ◽  
Mature Mirnas ◽  
Mirna Biogenesis ◽  
Sequencing Data ◽  
Whole Genome Analysis ◽  
Association Analyses ◽  
Genome Wide ◽  
Mirna Sequencing ◽  
And Function

Abstract BackgroundSNPs within pre-miRNA regions play a significant role in miRNA generation, processing and function by different molecular mechanisms and are thought to be major contributors to the variations in phenotypes and diseases. Therefore, whole-genome analysis of how SNPs affect mature miRNA biogenesis is important for precision medicine. ResultsIn this study, aiming to analyze the role of SNPs in mature miRNA biogenesis genome-wide, we constructed a SNP-pre-miRNA database, named miRSNPBase, consisting of 886 pre-miRNAs and 2640 SNPs based on the latest data. Then, we identified 10574 SNP-pre-miRNAs based on 886 pre-miRNAs and their associated 2640 SNPs, and we performed genome-wide association analyses to identify isoform miRNAs (isomiRs) based on miRFind that are associated with the mechanism of SNPs affecting miRNA maturation. A total of 4235 nor-SNP-pre-miRNAs based on 480 nor-pre-miRNAs and 1250 nor-SNPs were identified. We analyzed the effects of SNP type, SNP location and SNP-mediated free energy change during mature miRNA biogenesis and found that they are closely related to mature miRNA biogenesis. In addition, the MAF distribution of the iso-pre-miRNAs and nor-SNPs was analyzed based on the 1000 Genomes Project. The results demonstrated that individuals who contained the iso-SNPs were in the minority, and those who contained the nor-SNPs were in the majority. Notably, to verify our method and identify important biomarkers, we identified isomiRs and iso-SNPs in 18 GBR individuals of European origin. In the results, 209 iso-pre-miRNA candidates and 71 verified iso-pre-miRNAs of the 18 GBR samples were identified, and 2667 isomiRs of 209 pre-miRNAs were verified by miRNA sequencing data.ConclusionsOur results clearly indicated that SNPs that altered the mature miRNA splicing mechanism and led to the production of isomiRs, were closely related to and affected normal life processes, and led to epigenetic changes and diseases.

scholarly journals Role of ACE2/TMPRSS2 genes regulation by intestinal microRNA isoforms in the COVID-19 pathogenesis

2020 ◽  
Author(s):  
SA Nersisyan ◽  
MYu Shkurnikov ◽  
AI Osipyants ◽  
VI Vechorko
Keyword(s):  
Regulation Of Gene Expression ◽  
Surface Proteins ◽  
Sequencing Data ◽  
Angiotensin Converting Enzyme 2 ◽  
Mirna Sequencing ◽  
A Cell ◽  
Regulation Mechanisms ◽  
Transmembrane Serine Protease ◽  
High Level

Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.

scholarly journals Chandipura virus dysregulates the expression of hsa-miR-21-5p to activate NF-κB in human microglial cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Neha Pandey ◽  
Meghana Rastogi ◽  
Sunit K. Singh
Keyword(s):  
Expression Pattern ◽  
Case Fatality ◽  
Microglial Cells ◽  
Luciferase Assay ◽  
Western India ◽  
Cellular Mirnas ◽  
Over Expression ◽  
Chandipura Virus ◽  
Tnf Α

Abstract Background Chandipura virus (CHPV) is a negative single-stranded RNA virus of the Rhabdoviridae family. CHPV infection has been reported in Central and Western India. CHPV causes acute encephalitis with a case fatality rate of 70 % and mostly affects children below 15 years of age. CHPV infection in brain leads to neuronal apoptosis and activation of the microglial cells. The microRNAs (miRNAs) are small endogenous non-coding RNA that regulate the gene expression. Viral infections perturb the expression pattern of cellular miRNAs, which may in turn affect the expression pattern of downstream genes. This study aims to investigate hsa-miR-21-5p mediated regulation of PTEN, AKT, NF-ĸBp65, IL-6, TNF-α, and IL-1β, in human microglial cells during CHPV infection. Methods To understand the role of hsa-miR-21-5p in CHPV infection, the human microglial cells were infected with CHPV (MOI-0.1). Real-time PCR, western blotting, Luciferase assay, over-expression and knockdown techniques were used to understand the role of hsa-miR-21-5p in the regulation of PTEN, AKT and, NF-ĸBp65, IL-6, TNF-α, and IL-1β in this study. Results The hsa-miR-21-5p was found to be upregulated during CHPV infection in human microglial cells. This led to the downregulation of PTEN which promoted the phosphorylation of AKT and NF-ĸBp65. Over-expression of hsa-miR-21-5p led to the decreased expression of PTEN and promoted further phosphorylation of AKT and NF-ĸBp65 in human microglial cells. However, the inhibition of hsa-miR-21-5p using hsa-miR-21-5p inhibitor restored the expression. Conclusions This study supports the role of hsa-miR-21-5p in the regulation of pro-inflammatory genes in CHPV infected human microglial cells.

scholarly journals A protocol for adding knowledge to Wikidata: aligning resources on human coronaviruses

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Andra Waagmeester ◽  
Egon L. Willighagen ◽  
Andrew I. Su ◽  
Martina Kutmon ◽  
Jose Emilio Labra Gayo ◽  
...  
Keyword(s):  
Common Ground ◽  
Knowledge Bases ◽  
Public Knowledge ◽  
Medical Problems ◽  
Human Coronavirus ◽  
Data Schema ◽  
Helping Others ◽  
Human Coronaviruses ◽  
The Right ◽  
Human Coronavirus 229E

Abstract Background Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a “commons.” Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. Results As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. Conclusions Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).

scholarly journals Natural and Nature-Derived Products Targeting Human Coronaviruses

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 448
Author(s):  
Konstantina Vougogiannopoulou ◽  
Angela Corona ◽  
Enzo Tramontano ◽  
Michael N. Alexis ◽  
Alexios-Leandros Skaltsounis
Keyword(s):  
Natural Products ◽  
Antiviral Agents ◽  
Critical Perspective ◽  
Human Coronavirus ◽  
State Of Emergency ◽  
Pharmacological Agents ◽  
Pure Compounds ◽  
Total Plant ◽  
Human Coronaviruses ◽  
The 1960S

The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.

scholarly journals A new insight into role of phosphoketolase pathway in Synechocystis sp. PCC 6803

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anushree Bachhar ◽  
Jiri Jablonsky
Keyword(s):  
In Silico Analysis ◽  
Bioinformatic Analysis ◽  
Phosphoglycerate Mutase ◽  
Phosphoketolase Pathway ◽  
Multi Level ◽  
Silico Analysis ◽  
Insight Into ◽  
Synechocystis Sp ◽  
Pcc 6803

AbstractPhosphoketolase (PKET) pathway is predominant in cyanobacteria (around 98%) but current opinion is that it is virtually inactive under autotrophic ambient CO2 condition (AC-auto). This creates an evolutionary paradox due to the existence of PKET pathway in obligatory photoautotrophs. We aim to answer the paradox with the aid of bioinformatic analysis along with metabolic, transcriptomic, fluxomic and mutant data integrated into a multi-level kinetic model. We discussed the problems linked to neglected isozyme, pket2 (sll0529) and inconsistencies towards the explanation of residual flux via PKET pathway in the case of silenced pket1 (slr0453) in Synechocystis sp. PCC 6803. Our in silico analysis showed: (1) 17% flux reduction via RuBisCO for Δpket1 under AC-auto, (2) 11.2–14.3% growth decrease for Δpket2 in turbulent AC-auto, and (3) flux via PKET pathway reaching up to 252% of the flux via phosphoglycerate mutase under AC-auto. All results imply that PKET pathway plays a crucial role under AC-auto by mitigating the decarboxylation occurring in OPP pathway and conversion of pyruvate to acetyl CoA linked to EMP glycolysis under the carbon scarce environment. Finally, our model predicted that PKETs have low affinity to S7P as a substrate.

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