The analysis on the human protein domain targets and host-like interacting motifs for the MERS-CoV and SARS-CoV/CoV-2 infers the molecular mimicry of coronavirus

The MERS-CoV, SARS-CoV, and SARS-CoV-2 are highly pathogenic viruses that can cause severe pneumonic diseases in humans. Unfortunately, there is a non-available effective treatment to combat these viruses. Domain-motif interactions (DMIs) are an essential means by which viruses mimic and hijack the biological processes of host cells. To disentangle how viruses achieve this process can help to develop new rational therapies. Data mining was performed to obtain DMIs stored as regular expressions (regexp) in 3DID and ELM databases. The mined regexp information was mapped on the coronaviruses’ proteomes. Most motifs on viral protein that could interact with human proteins are shared across the coronavirus species, indicating that molecular mimicry is a common strategy for coronavirus infection. Enrichment ontology analysis for protein domains showed a shared biological process and molecular function terms related to carbon source utilization and potassium channel regulation. Some of the mapped motifs were nested on B, and T cell epitopes, suggesting that it could be as an alternative way for reverse vaccinology. The information obtained in this study could be used for further theoretic and experimental explorations on coronavirus infection mechanism and development of medicines for treatment.

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Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach

10.1101/2020.11.12.344424 ◽

2020 ◽

Author(s):

Hyunsu An ◽

Jihwan Park

Keyword(s):

T Cell ◽

Autoimmune Diseases ◽

Web Application ◽

Molecular Mimicry ◽

Sequence Similarity ◽

Protein Structures ◽

Cross Reactivity ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Human Proteins

ABSTRACTCurrently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.

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Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum

Journal of Biomedicine and Biotechnology ◽

10.1155/2008/326464 ◽

2008 ◽

Vol 2008 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

K.-Y. Hwa ◽

W. M. Lin ◽

Y.-I. Hou ◽

T.-M. Yeh

Keyword(s):

Sequence Homology ◽

Molecular Mimicry ◽

Lung Epithelial Cells ◽

Host Cells ◽

General Strategy ◽

Sars Coronavirus ◽

S Protein ◽

Lung Epithelial ◽

Human Proteins ◽

A Cell

Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS) is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV). The spike (S) protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937) and D08 (residues 942–951) were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502) stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.

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Targeting Viral Surface Proteins through Structure-Based Design

Viruses ◽

10.3390/v13071320 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1320

Author(s):

Yogesh B Narkhede ◽

Karen J Gonzalez ◽

Eva-Maria Strauch

Keyword(s):

Public Health ◽

Viral Infections ◽

Respiratory Viruses ◽

Surface Proteins ◽

Host Cells ◽

Viral Fusion ◽

Health It ◽

Viral Particles ◽

Pathogenic Viruses ◽

Viral Surface

The emergence of novel viral infections of zoonotic origin and mutations of existing human pathogenic viruses represent a serious concern for public health. It warrants the establishment of better interventions and protective therapies to combat the virus and prevent its spread. Surface glycoproteins catalyzing the fusion of viral particles and host cells have proven to be an excellent target for antivirals as well as vaccines. This review focuses on recent advances for computational structure-based design of antivirals and vaccines targeting viral fusion machinery to control seasonal and emerging respiratory viruses.

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SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽

10.3390/membranes11010064 ◽

2021 ◽

Vol 11 (1) ◽

pp. 64

Author(s):

Jordana Muñoz-Basagoiti ◽

Daniel Perez-Zsolt ◽

Jorge Carrillo ◽

Julià Blanco ◽

Bonaventura Clotet ◽

...

Keyword(s):

Viral Entry ◽

Ebola Virus ◽

Lessons Learned ◽

Productive Infection ◽

Target Cells ◽

Emerging Viruses ◽

Highly Pathogenic ◽

Life Threatening ◽

Pathogenic Viruses ◽

Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

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Antivirals with common targets against highly pathogenic viruses

Cell ◽

10.1016/j.cell.2021.02.013 ◽

2021 ◽

Vol 184 (6) ◽

pp. 1604-1620

Author(s):

Lu Lu ◽

Shan Su ◽

Haitao Yang ◽

Shibo Jiang

Keyword(s):

Highly Pathogenic ◽

Pathogenic Viruses

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Protection against Vaccinia Virus Challenge by CD8 Memory T Cells Resolved by Molecular Mimicry

Journal of Virology ◽

10.1128/jvi.01280-06 ◽

2006 ◽

Vol 81 (2) ◽

pp. 934-944 ◽

Cited By ~ 28

Author(s):

Markus Cornberg ◽

Brian S. Sheridan ◽

Frances M. Saccoccio ◽

Michael A. Brehm ◽

Liisa K. Selin

Keyword(s):

T Cells ◽

T Cell ◽

Vaccinia Virus ◽

Cd8 T Cells ◽

Protective Immunity ◽

Molecular Mimicry ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Epitopes ◽

Cell Responses

ABSTRACT Live vaccinia virus (VV) vaccination has been highly successful in eradicating smallpox. However, the mechanisms of immunity involved in mediating this protective effect are still poorly understood, and the roles of CD8 T-cell responses in primary and secondary VV infections are not clearly identified. By applying the concept of molecular mimicry to identify potential CD8 T-cell epitopes that stimulate cross-reactive T cells specific to lymphocytic choriomeningitis virus (LCMV) and VV, we identified after screening only 115 peptides two VV-specific immunogenic epitopes that mediated protective immunity against VV. An immunodominant epitope, VV-e7r130, did not generate cross-reactive T-cell responses to LCMV, and a subdominant epitope, VV-a11r198, did generate cross-reactive responses to LCMV. Infection with VV induced strong epitope-specific responses which were stable into long-term memory and peaked at the time virus was cleared, consistent with CD8 T cells assisting in the control of VV. Two different approaches, direct adoptive transfer of VV-e7r-specific CD8 T cells and prior immunization with a VV-e7r-expressing ubiquitinated minigene, demonstrated that memory CD8 T cells alone could play a significant role in protective immunity against VV. These studies suggest that exploiting cross-reactive responses between viruses may be a useful tool to complement existing technology in predicting immunogenic epitopes to large viruses, such as VV, leading to a better understanding of the role CD8 T cells play during these viral infections.

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The virome of German bats: comparing virus discovery approaches

Scientific Reports ◽

10.1038/s41598-021-86435-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Claudia Kohl ◽

Annika Brinkmann ◽

Aleksandar Radonić ◽

Piotr Wojtek Dabrowski ◽

Kristin Mühldorfer ◽

...

Keyword(s):

Virus Detection ◽

Detection Methods ◽

Single Type ◽

Metagenomic Sequencing ◽

Virus Discovery ◽

Highly Pathogenic ◽

Pcr Screening ◽

Specific Pcr ◽

Pathogenic Viruses ◽

Viral Sequences

AbstractBats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.

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An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

Frontiers in Microbiology ◽

10.3389/fmicb.2021.770935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liang Zhang ◽

Shuaiyin Chen ◽

Weiguo Zhang ◽

Haiyan Yang ◽

Yuefei Jin ◽

...

Keyword(s):

Animal Models ◽

Severe Acute Respiratory Syndrome ◽

Research Progress ◽

Laboratory Mice ◽

Disease Manifestation ◽

Highly Pathogenic ◽

The World ◽

Coronavirus Infection ◽

Different Levels ◽

Critical Aspects

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

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Mining the capacity of human-associated microorganisms to trigger rheumatoid arthritis—A systematic immunoinformatics analysis of T cell epitopes

PLoS ONE ◽

10.1371/journal.pone.0253918 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253918

Author(s):

Jelena Repac ◽

Marija Mandić ◽

Tanja Lunić ◽

Bojan Božić ◽

Biljana Božić Nedeljković

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

De Novo ◽

Molecular Mimicry ◽

Sequence Similarity ◽

Cell Epitope ◽

Homology Search ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Painful Condition

Autoimmune diseases, often triggered by infection, affect ~5% of the worldwide population. Rheumatoid Arthritis (RA)–a painful condition characterized by the chronic inflammation of joints—comprises up to 20% of known autoimmune pathologies, with the tendency of increasing prevalence. Molecular mimicry is recognized as the leading mechanism underlying infection-mediated autoimmunity, which assumes sequence similarity between microbial and self-peptides driving the activation of autoreactive lymphocytes. T lymphocytes are leading immune cells in the RA-development. Therefore, deeper understanding of the capacity of microorganisms (both pathogens and commensals) to trigger autoreactive T cells is needed, calling for more systematic approaches. In the present study, we address this problem through a comprehensive immunoinformatics analysis of experimentally determined RA-related T cell epitopes against the proteomes of Bacteria, Fungi, and Viruses, to identify the scope of organisms providing homologous antigenic peptide determinants. By this, initial homology screening was complemented with de novo T cell epitope prediction and another round of homology search, to enable: i) the confirmation of homologous microbial peptides as T cell epitopes based on the predicted binding affinity to RA-related HLA polymorphisms; ii) sequence similarity inference for top de novo T cell epitope predictions to the RA-related autoantigens to reveal the robustness of RA-triggering capacity for identified (micro/myco)organisms. Our study reveals a much larger repertoire of candidate RA-triggering organisms, than previously recognized, providing insights into the underestimated role of Fungi in autoimmunity and the possibility of a more direct involvement of bacterial commensals in RA-pathology. Finally, our study pinpoints Endoplasmic reticulum chaperone BiP as the most potent (most likely mimicked) RA-related autoantigen, opening an avenue for identifying the most potent autoantigens in a variety of different autoimmune pathologies, with possible implications in the design of next-generation therapeutics aiming to induce self-tolerance by affecting highly reactive autoantigens.

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Investigation of Various Diseases Occurred in Poultry and Management Strategies for Eradication

International Journal of Engineering & Technology ◽

10.14419/ijet.v7i3.1.17075 ◽

2018 ◽

Vol 7 (3.1) ◽

pp. 150

Author(s):

Sunil Patil ◽

Chhanwal I.L

Keyword(s):

Family Income ◽

Migratory Birds ◽

Management Practice ◽

Management Strategies ◽

Farm Management ◽

Poultry Meat ◽

Highly Pathogenic ◽

The World ◽

Pathogenic Viruses ◽

Poultry Disease

Poultry plays a significant role in the Indian economy. Around 60 billion chickens are raised per annum as a basis of food for both their eggs and meat. Poultry meat is in significant source of minerals, protein and various vitamins to balance the diet of human. Broiler farming is an important source of family income depending on size of the farm. Chicken farming in Commercial way is the most fruitful business in India and all around the world. Proper farm management practice and care of birds will result in decent profit in a short span of time. In this paper, we are discussing various diseases caused to poultry hen and their preventing or treating methods. Our results shows that some of disease cannot be cured and only it can be prevented. Spreading of disease with the help of contaminated equipment and infected poultry trade is measured as foremost means of spreading of poultry disease. In some countries migratory birds have also been foremost means of spreading of poultry disease like highly pathogenic viruses.

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