scholarly journals Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 360 ◽  
Author(s):  
Suhas Srinivasan ◽  
Hongzhu Cui ◽  
Ziyang Gao ◽  
Ming Liu ◽  
Senbao Lu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Experimental Research ◽  
Structural Genomics ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Research Community ◽  
Computational Pipeline ◽  
Functional Regions ◽  
Functional Differences ◽  
Novel Coronavirus

During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge, we leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline. As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community.

scholarly journals Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins

2020 ◽  
Author(s):  
Hongzhu Cui ◽  
Ziyang Gao ◽  
Ming Liu ◽  
Senbao Lu ◽  
Sun Mo ◽  
...  
Keyword(s):  
Structural Genomics ◽  
Molecular Mechanisms ◽  
Mainland China ◽  
Viral Proteins ◽  
Research Community ◽  
Computational Pipeline ◽  
Functional Regions ◽  
Functional Differences ◽  
Road Maps ◽  
Novel Coronavirus

AbstractDuring its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan

scholarly journals Structural Genomics and Interactomics of 2019 Wuhan Novel Coronavirus, SARS-CoV-2, Indicate Evolutionary Conserved Functional Regions of Viral Proteins

2020 ◽  
Author(s):  
Hongzhu Cui ◽  
Ziyang Gao ◽  
Ming Liu ◽  
Senbao Lu ◽  
Winnie Mkandawire ◽  
...  
Keyword(s):  
Structural Genomics ◽  
Molecular Mechanisms ◽  
Mainland China ◽  
Viral Proteins ◽  
Research Community ◽  
Computational Pipeline ◽  
Functional Regions ◽  
Functional Differences ◽  
Road Maps ◽  
Novel Coronavirus

During its first month, the recently emerged 2019 Wuhan novel coronavirus (SARS-CoV-2) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of SARS-CoV-2 and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan .

scholarly journals A proteomic model of SARS-COV2 infection by comparing the interactomes of BRD4 with BET-inhibition and SARS-COV2 viral proteins – implications for re-purposing approved drugs or ubiquitin-mediated degradation of select candidates

2020 ◽  
Author(s):  
GIRISH NALLUR
Keyword(s):  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Disease Diagnosis ◽  
Cellular Protein ◽  
Interacting Protein ◽  
Protein Targets ◽  
Us Fda ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Diagnosis Therapy

Abstract The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected 2,029,930 people worldwide and caused 136,320 deaths. Consequently, the hunt for drugs showing efficacy against this deadly disease, or vaccines for prevention, are being intensely investigated. Unfortunately, there is a scarcity of research data on the molecular mechanisms of SARS-CoV-2 infection for quickly finding effective therapies, or repurposing existing drugs approved by the US FDA. This report models existing knowledge of SARS-COV2 viral proteins and the cellular proteins they interact with by comparisons with BRD4 interacting proteins identified from B cells, with or without BET inhibition. The E protein of SARS-COV2 interacts with BRD4, and the Spike (S) protein with CANX. Extensive similarities were observed with published cellular interactants of 13 SARS-COV2 proteins resulting in 47 BRD4-interacting protein candidates, with or without BET inhibition. 61 cellular protein targets and 132 FDA approved drugs which use these proteins as targets are proposed, which can be investigated for efficacy against SARS-COV2 infections. The implications to SARS-COV2 disease diagnosis, therapy and vaccine creation are discussed.

scholarly journals The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2

2020 ◽  
Author(s):  
James Zhu ◽  
Jiwoong Kim ◽  
Xue Xiao ◽  
Yunguan Wang ◽  
Danni Luo ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Therapeutic Vaccine ◽  
Viral Proteins ◽  
Research Community ◽  
Minimum Loss ◽  
Bioinformatics Analyses ◽  
Complete Genomes ◽  
Novel Coronavirus

ABSTRACTThe outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas, or territories, causing staggering numbers of infections and deaths. In this study, bioinformatics analyses were performed on 5,568 complete genomes of SARS-CoV-2 virus to predict the T cell and B cell immunogenic epitopes of all viral proteins, which formed a systematic immune vulnerability landscape of SARS-CoV-2. The immune vulnerability and genetic variation profiles of SARS-CoV were compared with those of SARS-CoV and MERS-CoV. In addition, a web portal was developed to broadly share the data and results as a resource for the research community. Using this resource, we showed that genetic variations in SARS-CoV-2 are associated with loss of B cell immunogenicity, an increase in CD4+ T cell immunogenicity, and a minimum loss in CD8+ T cell immunogenicity, indicating the existence of a curious correlation between SARS-CoV-2 genetic evolutions and the immunity pressure from the host. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic/vaccine development and mechanistic research.

scholarly journals Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1597
Author(s):  
Olga V. Iarovaia ◽  
Elena S. Ioudinkova ◽  
Artem K. Velichko ◽  
Sergey V. Razin
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Viral Infection ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Infection Process ◽  
Regulatory Pathways ◽  
Nucleolar Proteins

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.

scholarly journals Molecular Insights on Potential Combination of Mapk Inhibitors Together with HCQ and HCQs Analogs in Viral Infection

2020 ◽  
Author(s):  
Tapan Kumar Mohanta ◽  
Nanaocha Sharma ◽  
Pietro Arina ◽  
Paola Defilippi
Keyword(s):  
Viral Infection ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
Specific Treatment ◽  
Molecular Data ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Approaches ◽  
Mapk Inhibitors ◽  
Novel Coronavirus

The outbreak of coronavirus disease-19 (COVID-19) has infected more than 11 million people and has claimed more than 530.000 deaths world-wide. In July 2020, still, there is no specific treatment for disease caused by the novel coronavirus. In the search to curb the global pandemic COVID-19, some eastern and developing countries have approved various treatment with controversial efficacy, among that the use of the antimalarial Hydroxychloroquine (HCQ), so far with inconclusive clinical evidence of effectiveness. On the other hand, computer-based screening suggest that HCQs analog are promising molecules, to impair viral replication in vitro[1]. Therefore, what is emerging from this complex background, is the need to understand molecular mechanism beyond drugs that can be helpful against viral infection for this and future pandemic. The intent of this Brief Report is to highlight: i) the involvement of the Mitogen Activated Protein Kinase (MAPK) cascade in viral infection and ii) the urgent need to have molecular data on the effectiveness of the combination of MAPK inhibitors together with HCQ and HCQs analogs in curbing viral infection. We are convinced that a better understanding of the patterns of elicited molecular mechanisms will be critical for new molecular approaches to this severe disease

Possible Targets and Therapies of SARS-CoV-2 Infection

2020 ◽  
Vol 20 (18) ◽  
pp. 1900-1907
Author(s):  
Kasturi Sarkar ◽  
Parames C. Sil ◽  
Seyed Fazel Nabavi ◽  
Ioana Berindan-Neagoe ◽  
Cosmin Andrei Cismaru ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Infection ◽  
Human Activity ◽  
Viral Proteins ◽  
Therapeutic Agents ◽  
Effective Control ◽  
Human Society ◽  
Global Spread ◽  
Repurposed Drugs

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.

scholarly journals Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 706
Author(s):  
Antonio J. Moreno-Pérez ◽  
Raquel Martins-Noguerol ◽  
Cristina DeAndrés-Gil ◽  
Mónica Venegas-Calerón ◽  
Rosario Sánchez ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
Acid Synthesis ◽  
Sunflower Seeds ◽  
Acid Biosynthesis ◽  
Functional Regions ◽  
Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

scholarly journals Value-added and Transparent Experiments

2021 ◽  
pp. 147892992110594
Author(s):  
Peter John Loewen ◽  
Daniel Rubenson
Keyword(s):  
Experimental Research ◽  
Large Range ◽  
Value Added ◽  
Research Community ◽  
Future Research ◽  
Political Elites ◽  
Important Work ◽  
Simple Rules ◽  
Combined Features ◽  
Public Scrutiny

Experimental research by political scientists on elites has grown dramatically in recent years. Experimenting on and with elites raises important questions, both practical and ethical. Elites are busy people, doing important work under public scrutiny. Therefore, any experiments that use up political elites’ time, risk impairing their ability to do their jobs as well as possible, or put at risk the larger research community’s access to elites should be avoided. Nevertheless, despite these risks and challenges, we argue experimenting with elites has enough benefits both to the research community and to elites themselves, that it should still be done. The relevant question then becomes how should we think about doing experiments with political elites? We propose a framework of value-added and transparent experiments. Our framework is guided by the following two simple rules: Elite subjects should individually benefit from the process of doing the experiment. It should add value to their role as representatives. Second, the identity of the researchers and purposes of the experiment should be transparent. As we argue, these two combined features can still accommodate a large range of experiments, can creatively spark researchers to think up new designs and can protect access to elites for future research. We review two such examples at the end of this essay.

scholarly journals Development of Web Application for the Comparison of Segment Variability with Sequence Evolution and Immunogenic Properties for Highly Variable Proteins: An Application to Viruses

2021 ◽  
Author(s):  
Sumit Bala ◽  
Ambarnil Ghosh ◽  
Subhra Pradhan
Keyword(s):  
Experimental Research ◽  
Web Application ◽  
Structural Information ◽  
Solvent Accessibility ◽  
Viral Proteins ◽  
High Rate ◽  
Survival Strategies ◽  
Host Immune System ◽  
Application Development ◽  
The Web

AbstractHigh rate of mutation and structural flexibilities in viral proteins quickly make them resistant to the host immune system and existing antiviral strategies. For most of the pathogenic viruses, the key survival strategies lie in their ability to evolve rapidly through mutations that affects the protein structure and function. Along with the experimental research related to antiviral development, computational data mining also plays an important role in deciphering the molecular and genomic signatures of the viral adaptability. Uncovering conserved regions in viral proteins with diverse chemical and biological properties is an important area of research for developing antiviral therapeutics, though assigning those regions is not a trivial work. Advancement in protein structural information databases and repositories, made by experimental research accelerated the in-silico mining of the data to generate more integrative information. Despite of the huge effort on correlating the protein structural information with its sequence, it is still a challenge to defeat the high mutability and adaptability of the viral genomics structure. In this current study, the authors have developed a user-friendly web application interface that will allow users to study and visualize protein segment variabilities in viral proteins and may help to find antiviral strategies. The present work of web application development allows thorough mining of the surface properties and variabilities of viral proteins which in combination with immunogenicity and evolutionary properties make the visualization robust. In combination with previous research on 20-Dimensional Euclidian Geometry based sequence variability characterization algorithm, four other parameters has been considered for this platform: [1] predicted solvent accessibility information, [2] B-Cell epitopic potential, [3] T-Cell epitopic potential and [4] coevolving region of the viral protein. Uniqueness of this study lies in the fact that a protein sequence stretch is being characterized rather than single residue-based information, which helps to compare properties of protein segments with variability. In current work, as an example, beside presenting the web application platform, five proteins of SARS-CoV2 was presented with keeping focus on protein-S. Current web-application database contains 29 proteins from 7 viruses including a GitHub repository of the raw data used in this study. The web application is up and running in the following address: http://www.protsegvar.com.

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