scholarly journals Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions

2020 ◽  
Author(s):  
Jayanta Kumar Das ◽  
Subhadip Chakraborty ◽  
Swarup Roy
Keyword(s):  
Codon Usage ◽  
Signaling Pathways ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Viral Protein ◽  
Viral Proteins ◽  
Host Protein ◽  
Host Proteins ◽  
Disease Pathogenesis ◽  
Pattern Similarity

AbstractUnderstanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploiting the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.Extensive analysis performed to understand the network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins, mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.

scholarly journals Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

2015 ◽  
Vol 90 (4) ◽  
pp. 1973-1987 ◽  
Author(s):  
Stacy L. DeBlasio ◽  
Juan D. Chavez ◽  
Mariko M. Alexander ◽  
John Ramsey ◽  
Jimmy K. Eng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Interaction Network ◽  
Host Protein ◽  
Host Proteins ◽  
Content Type ◽  
Host Pathogen ◽  
Pathogen Protein ◽  
Binding Interfaces

ABSTRACTDemonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus[PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in theLuteoviridaeand with unrelated viruses in theHerpesviridaeandAdenoviridae. Functional analysis of three PLRV-interacting host proteinsin plantausing a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies.IMPORTANCEThe exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used protein interaction reporter (PIR) technology to illustrate how viruses exploit host proteins during plant infection. PIR technology enabled our team to precisely describe the sites of functional virus-virus, virus-host, and host-host protein interactions using a mass spectrometry analysis that takes just a few hours. Applications of PIR technology in host-pathogen interactions will enable researchers studying recalcitrant pathogens, such as animal pathogens where host proteins are incorporated directly into the infectious agents, to investigate how proteins interact during infection and transmission as well as develop new tools for interdiction and therapy.

scholarly journals A SARS-CoV-2 – host proximity interactome

2020 ◽  
Author(s):  
Payman Samavarchi-Tehrani ◽  
Hala Abdouni ◽  
James D.R. Knight ◽  
Audrey Astori ◽  
Reuben Samson ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein Interactions ◽  
Affinity Purification ◽  
Drug Repurposing ◽  
Viral Proteins ◽  
Host Protein ◽  
Virus Protein ◽  
Host Proteins ◽  
Biochemical Purification ◽  
Cell Functions

AbstractViral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.

scholarly journals Different Subtypes of Influenza Viruses Target Different Human Proteins and Pathways Leading to Different Pathogenic Phenotypes

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yujie Wang ◽  
Ting Song ◽  
Kaiwu Li ◽  
Yuan Jin ◽  
Junjie Yue ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Viral Proteins ◽  
Influenza Viruses ◽  
Host Protein ◽  
Protein Protein Interactions ◽  
Influenza A Viruses ◽  
Host Proteins ◽  
Pathogenic Mechanisms ◽  
Human Proteins

Different subtypes of influenza A viruses (IAVs) cause different pathogenic phenotypes after infecting human bodies. Analysis of the interactions between viral proteins and the host proteins may provide insights into the pathogenic mechanisms of the virus. In this paper, we found that the same proteins (nucleoprotein and neuraminidase) of H1N1 and H5N1 have different impacts on the NF-κB activation. By further examining the virus–host protein–protein interactions, we found that both NP and NA proteins of the H1N1 and H5N1 viruses target different host proteins. These results indicate that different subtypes of influenza viruses target different human proteins and pathways leading to different pathogenic phenotypes.

scholarly journals Viruses.STRING: A virus–host protein–protein interaction database

2018 ◽  
Author(s):  
Helen Victoria Cook ◽  
Nadezhda Tsankova ◽  
Damian Szklarczyk ◽  
Christian von Mering ◽  
Lars Juhl Jensen
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Host Protein ◽  
Interaction Data ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Host Interactions ◽  
Protein Protein Interaction ◽  
Interaction Database ◽  
Protein Interaction Database

AbstractAs viruses continue to pose risks to global health, having a better un-derstanding of virus–host protein–protein interactions aids in the development of treatments and vaccines. Here, we introduce Viruses.STRING, a protein–protein interaction database specifically catering to virus-virus and virus-host interactions. This database combines evidence from experimental and text-mining channels to provide combined probabilities for interactions between viral and host proteins. The database contains 177,425 interactions between 239 viruses and 319 hosts. The database is publicly available at viruses.string-db.org, and the interaction data can also be accessed through the latest version of the Cytoscape STRING app.

scholarly journals Viruses.STRING: A Virus-Host Protein-Protein Interaction Database

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 519 ◽  
Author(s):  
Helen Cook ◽  
Nadezhda Doncheva ◽  
Damian Szklarczyk ◽  
Christian von Mering ◽  
Lars Jensen
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Host Protein ◽  
Interaction Data ◽  
Protein Protein Interactions ◽  
Host Proteins ◽  
Host Interactions ◽  
Protein Protein Interaction ◽  
Interaction Database ◽  
Protein Interaction Database

As viruses continue to pose risks to global health, having a better understanding of virus–host protein–protein interactions aids in the development of treatments and vaccines. Here, we introduce Viruses.STRING, a protein–protein interaction database specifically catering to virus–virus and virus–host interactions. This database combines evidence from experimental and text-mining channels to provide combined probabilities for interactions between viral and host proteins. The database contains 177,425 interactions between 239 viruses and 319 hosts. The database is publicly available at viruses.string-db.org, and the interaction data can also be accessed through the latest version of the Cytoscape STRING app.

scholarly journals Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 897
Author(s):  
Ernesto Estrada
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Interactions ◽  
Molecular Level ◽  
Direct Consequence ◽  
Viral Proteins ◽  
Clinical Findings ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Bioinformatic Tools

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson’s disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

scholarly journals Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 283
Author(s):  
Michael D. Barrera ◽  
Victoria Callahan ◽  
Ivan Akhrymuk ◽  
Nishank Bhalla ◽  
Weidong Zhou ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Trafficking ◽  
Viral Protein ◽  
Sindbis Virus ◽  
Encephalitis Virus ◽  
Host Proteins ◽  
Atp Production ◽  
Equine Encephalitis Virus ◽  
E2 Glycoprotein ◽  
Late Stages

Alphaviruses are a genus of the Togaviridae family and are widely distributed across the globe. Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), cause encephalitis and neurological sequelae while chikungunya virus (CHIKV) and Sindbis virus (SINV) cause arthralgia. There are currently no approved therapeutics or vaccines available for alphaviruses. In order to identify novel therapeutics, a V5 epitope tag was inserted into the N-terminus of the VEEV E2 glycoprotein and used to identify host-viral protein interactions. Host proteins involved in protein folding, metabolism/ATP production, translation, cytoskeleton, complement, vesicle transport and ubiquitination were identified as VEEV E2 interactors. Multiple inhibitors targeting these host proteins were tested to determine their effect on VEEV replication. The compound HA15, a GRP78 inhibitor, was found to be an effective inhibitor of VEEV, EEEV, CHIKV, and SINV. VEEV E2 interaction with GRP78 was confirmed through coimmunoprecipitation and colocalization experiments. Mechanism of action studies found that HA15 does not affect viral RNA replication but instead affects late stages of the viral life cycle, which is consistent with GRP78 promoting viral assembly or viral protein trafficking.

scholarly journals A map of direct SARS-CoV-2 protein interactions implicates specific human host processes

2021 ◽  
Author(s):  
Dae-Kyum Kim ◽  
Benjamin Weller ◽  
Chung-Wen Lin ◽  
Dayag Sheykhkarimli ◽  
Jennifer J Knapp ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Membrane Trafficking ◽  
Host Protein ◽  
Host Proteins ◽  
Systematic Map ◽  
High Data ◽  
Protein Ubiquitination ◽  
Human Proteins ◽  
Physical Interactions ◽  
Key Steps

Key steps in viral propagation, immune suppression and pathology are mediated by direct, binary physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary physical interactions between viral and host interactions, complementing previous co-complex association maps by conveying more direct mechanistic understanding and enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, with orthogonal validation by an internally benchmarked NanoLuc two-hybrid system to ensure high data quality. Host proteins interacting with SARS-CoV-2 proteins were enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The direct virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.

scholarly journals Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions

2021 ◽  
Author(s):  
Ernesto Estrada
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Interactions ◽  
Molecular Level ◽  
Direct Consequence ◽  
Viral Proteins ◽  
Clinical Findings ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Bioinformatic Tools

Abstract Background : Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson's disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD some hypothesis have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients in general and for the PD cases reported in particular. Given the importance of this potential connection we present here a molecular-level mechanism that explain well these findings and will serve to explore the potential CNS damage in COVID-19 patients. Methods : A model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Results : We found 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. Conclusions : The molecular-level mechanism presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

scholarly journals BIOINFORMATICS APPROACH ON ACTION AND MECHANISM OF BROMELAIN IN HEPATOCELLULAR CARCINOMA

2021 ◽  
pp. 122-129
Author(s):  
SUSHMA S MURTHY ◽  
BALA NARSAIAH T
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Interaction Network ◽  
P53 Gene ◽  
Computational Method ◽  
Mesenchymal Transition ◽  
In Silico Studies ◽  
Data Points

Objective: The objective of the study was to understand biomolecular interactions of Bromelain and its networking with p53 and β-catenin by a computational method of analysis in Hepatocellular carcinoma (HCC) condition. Methodology: The protein interaction partners for p53 and β-catenin involved in the progression of HCC were collected from National Center for Biotechnology Information. We collected data points and standardized the data points for our data analysis from the public database. We used Cytoscape 3.8.2 version plug-in for constructing a Protein-Protein interaction network. We constructed a pathway network using Biorender.com. Results: The protein interactions concerning p53 and β-catenin are identified and a network is constructed. A total of 18 and 34 nodes were identified which are involved in down-regulation and up-regulation of β-catenin and a total of 30 and 27 nodes for homosapiens are identified which are involved in the downregulation and upregulation of the p53 gene. We identified different pathways which trigger and impact the p53 and Wnt/β- catenin signaling pathways as potential target sites for Bromelain to arrest the progression of cancer Conclusion: In conclusion, our in silico studies anti-cancer activity of Bromelain in HCC relating its effect on apoptosis, cell differentiation, mesenchymal transition, p53 signaling, and Wnt/β-catenin signaling pathways.

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