SARS-CoV-2 spike protein displays sequence similarities with paramyxovirus surface proteins; a bioinformatics study

Recent emergence of SARS-CoV-2 and associated COVID-19 pandemic have posed a great challenge for the scientific community. In this study, we performed bioinformatic analyses on SARS-CoV-2 protein sequences, trying to unravel potential molecular similarities between this newly emerged pathogen with non-coronavirus ssRNA viruses. Comparing the proteins of SARS-CoV-2 with non-coronavirus positive and negative strand ssRNA viruses revealed multiple sequence similarities between SARS-CoV-2 and non-coronaviruses, including similarities between RNA-dependent RNA-polymerases and helicases (two highly-conserved proteins). We also observed similarities between SARS-CoV-2 surface (i.e. spike) protein with paramyxovirus fusion proteins. This similarity was restricted to a segment of spike protein S2 subunit which is involved in cell fusion. We next analyzed spike proteins from SARS-CoV-2 “variants of concern” (VOCs) and “variants of interests” (VOIs) and found that some of these variants show considerably higher spike-fusion similarity with paramyxoviruses. The ‘spike-fusion’ similarity was also observed for some pathogenic coronaviruses other than SARS-CoV-2. Epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that several B cell epitopes as well as T cell and MHC binding epitopes map within the spike-fusion similarity region. These data indicate that there might be a degree of convergent evolution between SARS-CoV-2 and paramyxovirus surface proteins which could be of pathogenic and immunological importance.

Identification of Novel Candidate CD8+ T Cell Epitopes of the SARS-CoV2 with Homology to Other Seasonal Coronaviruses

Cross-reactive T cell immunity to seasonal coronaviruses (HCoVs) may lead to immunopathology or protection during SARS-CoV2 infection. To understand the influence of cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8+ T cell epitopes, restricted through HLA-A and B alleles. Conservation analysis was carried out for these epitopes with HCoVs, OC43, HKU1, and NL63. 12/18 the candidate CD8+ T cell epitopes (binding score of ≥0.90), which had a high degree of homology (>75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206, and HLA-B alleles B*3501. Thirty-one candidate CD8+ T cell epitopes that were specific to SARS-CoV2 virus (<25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane, and nucleocapsid) and the NSP1, NSP2, and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403 (7/31), and HLA-A*2402 (8/31). It would be crucial to understand T cell responses that associate with protection, and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups, to understand disease pathogenesis.

An immunologically friendly classification of non-peptidic ligands

The Immune Epitope Database (IEDB) freely provides experimental data regarding immune epitopes to the scientific public. The main users of the IEDB are immunologists who can easily use our web interface to search for peptidic epitopes via their simple single-letter codes. For example, ‘A’ stands for ‘alanine’. Similarly, users can easily navigate the IEDB’s simplified NCBI taxonomy hierarchy to locate proteins from specific organisms. However, some epitopes are non-peptidic, such as carbohydrates, lipids, chemicals and drugs, and it is more challenging to consistently name them and search upon, making access to their data more problematic for immunologists. Therefore, we set out to improve access to non-peptidic epitope data in the IEDB through the simplification of the non-peptidic hierarchy used in our search interfaces. Here, we present these efforts and their outcomes. Database URL: http://www.iedb.org/

An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-CoV-2

COVID-19 is a new viral emergent disease caused by a novel strain of coronavirus. This virus has caused a huge problem in the world as millions of people are affected by this disease. We aimed at designing a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system. The envelope protein sequence of SARS-CoV-2 has been retrieved from the NCBI database. The bioinformatics analysis was carried out by using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. The predicted HTL and CTL epitopes were docked with HLA alleles and binding energies were evaluated. The allergenicity of predicted epitopes was analyzed, the conservancy analysis was performed, and the population coverage was determined throughout the world. Some overlapped CTL, HTL, and B-cell epitopes were suggested to become a universal candidate for peptide-based vaccine against COVID-19. This vaccine peptide could simultaneously elicit humoral and cell-mediated immune responses. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate.

Vaccines against Covid-19: the Comparative Estimates of Risks in Adenovirus Vectors

Relevance. The vaccine against the SARS-Cov-2 coronavirus is considered as the most promising approach to curb (tame) a current pandemic and prevent new one. Three vaccines (AstraZeneca’s СhAdOx1 nCov-19, CanSino’s vaccine and Russia’s Sputnik V one) are in Phase III clinical trials and have the S protein as immunogen but different adenovirus vectors. It is known adverse neurological events associated with the СhAdOx1 nCov-19 vacсine.Aim is to investigate the distribution of homologous sequences of adenovirus proteins in human nervous and immune systems proteins, estimate potential risks of using adenovirus vectors in vaccines and discuss possible mechanisms inducing immune damage in the nervous system.Materials and methods. For the computer analysis of peptide (immune epitope) relationship between adenovirus structural proteins and human proteins, the search of homologous sequences was made. All protein sequences were used from databases available on the INTERNET.Results. Among adenoviruses (НАд5, НАд26 , ChАдY25, and SAd3) ChАдY25 has the highest content of sequences homologous to human nervous system proteins that may be the cause of autoimmune complications in vaccination.Conclusion: In AstraZeneca’s СhAdOx1 nCov-19 vaccine there are a large number of peptide sequences homologous to human nervous system proteins and it allows to predict the possible risks with this vaccine.

Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19

Interleukin 6 (IL-6) is a pro-inflammatory cytokine that stimulates acute phase responses, hematopoiesis and specific immune reactions. Recently, it was found that the IL-6 plays a vital role in the progression of COVID-19, which is responsible for the high mortality rate. In order to facilitate the scientific community to fight against COVID-19, we have developed a method for predicting IL-6 inducing peptides/epitopes. The models were trained and tested on experimentally validated 365 IL-6 inducing and 2991 non-inducing peptides extracted from the immune epitope database. Initially, 9149 features of each peptide were computed using Pfeature, which were reduced to 186 features using the SVC-L1 technique. These features were ranked based on their classification ability, and the top 10 features were used for developing prediction models. A wide range of machine learning techniques has been deployed to develop models. Random Forest-based model achieves a maximum AUROC of 0.84 and 0.83 on training and independent validation dataset, respectively. We have also identified IL-6 inducing peptides in different proteins of SARS-CoV-2, using our best models to design vaccine against COVID-19. A web server named as IL-6Pred and a standalone package has been developed for predicting, designing and screening of IL-6 inducing peptides (https://webs.iiitd.edu.in/raghava/il6pred/).

SARS-CoV2 spike protein displays biologically significant similarities with paramyxovirus surface proteins; a bioinformatics study

Recent emergence of SARS-CoV2 and associated COVID-19 pandemic has posed a great challenge for the scientific community. Understanding various aspects of SARS-CoV2 biology, virulence and pathogenesis as well as determinants of immune response have become a global research priority. In this study, we performed bioinformatic analyses on SAR-CoV2 protein sequences, trying to unravel biologically important similarities between this newly emerged virus with other RNA viruses. Comparing the proteome of SARS-CoV2 with major positive and negative strand ssRNA viruses showed significant homologies between SARS-CoV2 spike protein with pathogenic paramyxovirus fusion proteins. This ‘spike-fusion’ homology was not limited to SARS-CoV2 and it existed for some other pathogenic coronaviruses; nonetheless, SARS-CoV2 spike-fusion homology was orders of magnitude stronger than homologies observed for other known coronaviruses. Moreover, this homology did not seem to be a consequence of general ssRNA virus phylogenetic relations. We also explored potential immunological significance of this spike-fusion homology. Spike protein epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that the majority of spike’s T cell epitopes as well as many B cell and MHC binding epitopes map within the spike-fusion homology region. Overall, our data indicate that there might be a relation between SARS-CoV2 and paramyxoviruses at the level of their surface proteins and this relation could be of crucial immunological importance.

From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry

Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic.

Molecular Epidemiology of B3 and D8 Measles Viruses through Hemagglutinin Phylogenetic History

Of the 24 known measles genotypes, only D8 and B3 are responsible for outbreaks in the last years in Europe, Asia, and America. In this study the H gene of 92 strains circulating between 2015 and 2019 in Lombardy, Northern Italy, and 1273 H sequences available in GenBank were analyzed in order to evaluate the genetic variability and to assess the conservation of the immunodominant sites. Overall, in Lombardy we observed the presence of four different B3 and three different D8 clusters, each one of them including sequences derived from viruses found in both vaccinated and unvaccinated subjects. Worldwide, the residue 400 within the H protein, a position located within the main immune epitope, is mutated in all circulating strains that belong to the two globally endemic genotypes, B3 and D8. Our data demonstrate the usefulness of measles virus (MV) H gene sequencing. Indeed, the monitoring the H protein epitopes of circulating strains could be included in the measles laboratory surveillance activities in order to improve and optimize strategies for measles control, as countries go towards elimination phase.