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1.
Viruses ; 12(7)2020 07 14.
Article in English | MEDLINE | ID: covidwho-649596

ABSTRACT

Next-generation sequencing (NGS) offers a powerful opportunity to identify low-abundance, intra-host viral sequence variants, yet the focus of many bioinformatic tools on consensus sequence construction has precluded a thorough analysis of intra-host diversity. To take full advantage of the resolution of NGS data, we developed HAplotype PHylodynamics PIPEline (HAPHPIPE), an open-source tool for the de novo and reference-based assembly of viral NGS data, with both consensus sequence assembly and a focus on the quantification of intra-host variation through haplotype reconstruction. We validate and compare the consensus sequence assembly methods of HAPHPIPE to those of two alternative software packages, HyDRA and Geneious, using simulated HIV and empirical HIV, HCV, and SARS-CoV-2 datasets. Our validation methods included read mapping, genetic distance, and genetic diversity metrics. In simulated NGS data, HAPHPIPE generated pol consensus sequences significantly closer to the true consensus sequence than those produced by HyDRA and Geneious and performed comparably to Geneious for HIV gp120 sequences. Furthermore, using empirical data from multiple viruses, we demonstrate that HAPHPIPE can analyze larger sequence datasets due to its greater computational speed. Therefore, we contend that HAPHPIPE provides a more user-friendly platform for users with and without bioinformatics experience to implement current best practices for viral NGS assembly than other currently available options.


Subject(s)
Computational Biology/methods , High-Throughput Nucleotide Sequencing/methods , Viruses/genetics , Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Genomics/methods , HIV/genetics , Haplotypes , Hepacivirus/genetics , Humans , Pandemics , Pneumonia, Viral/virology
2.
Sci Rep ; 10(1): 14179, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-741695

ABSTRACT

A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.


Subject(s)
Betacoronavirus/immunology , Computational Biology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Proteins/immunology , Amino Acid Sequence , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/metabolism , Computational Biology/methods , Coronavirus Infections/metabolism , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Genome, Viral , Genomics/methods , Humans , Models, Molecular , Pandemics , Peptides/chemistry , Peptides/immunology , Phylogeny , Pneumonia, Viral/metabolism , Structure-Activity Relationship , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccines, Subunit/immunology , Viral Proteins/chemistry , Viral Vaccines/immunology
3.
Aging (Albany NY) ; 12(15): 15784-15796, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-721666

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an epidemic disease characterized by rapid infection and a high death toll. The clinical diagnosis of patients with COVID-19 has risen sharply, especially in Western countries. Globally, an effective treatment for COVID-19 is still limited. Vitamin A (VA) exhibits pharmacological activity in the management of pneumonia. Thus, we reason that VA may potentially serve as an anti-SARS-CoV-2 regimen. In this study, bioinformatics analysis and computation assays using a network pharmacology method were conducted to explore and uncover the therapeutic targets and mechanisms of VA for treating COVID-19. We identified candidate targets, pharmacological functions, and therapeutic pathways of VA against SARS-CoV-2. Bioinformatics findings indicate that the mechanisms of action of VA against SARS-CoV-2 include enrichment of immunoreaction, inhibition of inflammatory reaction, and biological processes related to reactive oxygen species. Furthermore, seven core targets of VA against COVID-19, including MAPK1, IL10, EGFR, ICAM1, MAPK14, CAT, and PRKCB were identified. With this bioinformatics-based report, we reveal, for the first time, the anti-SARS-CoV-2 functions and mechanisms of VA and suggest that VA may act as a potent treatment option for COVID-19, a deadly global epidemic.


Subject(s)
Betacoronavirus , Coronavirus Infections , Immunity/drug effects , Inflammation , Pandemics , Pneumonia, Viral , Vitamin A , Betacoronavirus/drug effects , Betacoronavirus/genetics , Betacoronavirus/physiology , Biological Availability , Computational Biology/methods , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Gene Ontology , Humans , Inflammation/drug therapy , Inflammation/etiology , Inflammation/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Signal Transduction/drug effects , Vitamin A/pharmacokinetics , Vitamin A/therapeutic use , Vitamins/pharmacokinetics , Vitamins/therapeutic use
4.
Sci Rep ; 10(1): 13866, 2020 08 17.
Article in English | MEDLINE | ID: covidwho-720849

ABSTRACT

The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein - ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.


Subject(s)
Betacoronavirus/drug effects , Computational Biology/methods , Coronavirus Infections/metabolism , Drug Discovery/methods , Drug Repositioning/methods , Pneumonia, Viral/metabolism , Aminopyridines/pharmacology , Benzodioxoles/pharmacology , Betacoronavirus/chemistry , Binding Sites , Coronavirus Infections/virology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Protein Binding/drug effects , Protein Conformation , Protein Domains/drug effects , Protein Interaction Maps/drug effects , Simeprevir/pharmacology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism
5.
Infect Dis Poverty ; 9(1): 88, 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-690345

ABSTRACT

BACKGROUND: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. METHODS: The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. RESULTS: A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315-324, Spike333-338, Spike648-663, Spike1064-1079) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC class I and MHC class II molecules respectively. The peptides (Nucleocapsid66-75, Nucleocapsid104-112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. CONCLUSIONS: B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Computational Biology/methods , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Amino Acid Sequence , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Design , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Humans , Immunogenicity, Vaccine/immunology , Models, Molecular , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Sequence Alignment , Sequence Analysis , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Envelope Proteins/immunology
6.
J Virol ; 94(18)2020 08 31.
Article in English | MEDLINE | ID: covidwho-639244

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Genetic Variation , Genome, Viral , Genomics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Amino Acid Substitution , Betacoronavirus/classification , Computational Biology/methods , Coronavirus Infections/transmission , Genomics/methods , Humans , Mexico/epidemiology , Mutation , Pandemics , Phylogeny , Pneumonia, Viral/transmission
7.
J Transl Med ; 18(1): 281, 2020 07 10.
Article in English | MEDLINE | ID: covidwho-639103

ABSTRACT

BACKGROUND: The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. METHODS: Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, and Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratope binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. RESULTS: We screened here few pairs of spike protein epitopic regions and selected their energetic, Inhibitory Concentration50 (IC50), MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. CONCLUSION: The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.


Subject(s)
Betacoronavirus/immunology , Computational Biology/methods , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Amino Acid Motifs , Amino Acid Sequence , Conserved Sequence , Coronavirus Infections/prevention & control , Glycosylation , Histocompatibility Antigens Class II/metabolism , Humans , Inhibitory Concentration 50 , Molecular Sequence Annotation , Pandemics , Protein Structure, Secondary , Spike Glycoprotein, Coronavirus/chemistry
8.
Genes (Basel) ; 11(7)2020 07 03.
Article in English | MEDLINE | ID: covidwho-636017

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.


Subject(s)
Coronavirus Infections/pathology , European Continental Ancestry Group/genetics , Genetic Variation , Nervous System Diseases/complications , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/pathology , Betacoronavirus/isolation & purification , Brain/metabolism , Computational Biology/methods , Coronavirus Infections/complications , Coronavirus Infections/virology , Genotype , Humans , Italy , Nervous System Diseases/pathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Polymorphism, Single Nucleotide , Quantitative Trait Loci
9.
PLoS Comput Biol ; 16(7): e1008031, 2020 07.
Article in English | MEDLINE | ID: covidwho-624431

ABSTRACT

The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.


Subject(s)
Contact Tracing/methods , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Forecasting/methods , Models, Statistical , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Age Factors , Asymptomatic Infections/epidemiology , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , China/epidemiology , Computational Biology/methods , Disease Outbreaks/prevention & control , Humans , Pandemics/prevention & control , Pandemics/statistics & numerical data , Virus Replication/physiology
10.
PLoS Comput Biol ; 16(7): e1007990, 2020 07.
Article in English | MEDLINE | ID: covidwho-628823

ABSTRACT

The effective reproduction number, Rt, is a key time-varying prognostic for the growth rate of any infectious disease epidemic. Significant changes in Rt can forewarn about new transmissions within a population or predict the efficacy of interventions. Inferring Rt reliably and in real-time from observed time-series of infected (demographic) data is an important problem in population dynamics. The renewal or branching process model is a popular solution that has been applied to Ebola and Zika virus disease outbreaks, among others, and is currently being used to investigate the ongoing COVID-19 pandemic. This model estimates Rt using a heuristically chosen piecewise function. While this facilitates real-time detection of statistically significant Rt changes, inference is highly sensitive to the function choice. Improperly chosen piecewise models might ignore meaningful changes or over-interpret noise-induced ones, yet produce visually reasonable estimates. No principled piecewise selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory, which deems the model capable of describing the observed data using the fewest bits as most justified. We derive exact posterior prediction distributions for infected population size and integrate these within an APE framework to obtain an exact and reliable method for identifying the piecewise function best supported by available epidemic data. We find that this choice optimises short-term prediction accuracy and can rapidly detect salient fluctuations in Rt, and hence the infected population growth rate, in real-time over the course of an unfolding epidemic. Moreover, we emphasise the need for formal selection by exposing how common heuristic choices, which seem sensible, can be misleading. Our APE-based method is easily computed and broadly applicable to statistically similar models found in phylogenetics and macroevolution, for example. Our results explore the relationships among estimate precision, forecast reliability and model complexity.


Subject(s)
Computational Biology/methods , Coronavirus Infections/epidemiology , Forecasting/methods , Models, Statistical , Pneumonia, Viral/epidemiology , Betacoronavirus/physiology , Coronavirus Infections/virology , Disease Outbreaks/prevention & control , Humans , Information Theory , Pandemics , Pneumonia, Viral/virology , Reproducibility of Results , Virus Replication/physiology
11.
Microbes Infect ; 22(4-5): 182-187, 2020.
Article in English | MEDLINE | ID: covidwho-626674

ABSTRACT

Envelope protein of coronaviruses is a structural protein existing in both monomeric and homo-pentameric form. It has been related to a multitude of roles including virus infection, replication, dissemination and immune response stimulation. In the present study, we employed an immunoinformatic approach to investigate the major immunogenic domains of the SARS-CoV-2 envelope protein and map them among the homologue proteins of coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Also, when not available, we predicted the envelope protein structural folding and mapped SARS-CoV-2 epitopes. Envelope sequences alignment provides evidence of high sequence homology for some of the investigated virus specimens; while the structural mapping of epitopes resulted in the interesting maintenance of the structural folding and epitope sequence localization also in the envelope proteins scoring a lower alignment score. In line with the One-Health approach, our evidences provide a molecular structural rationale for a potential role of taxonomically related coronaviruses in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.


Subject(s)
Betacoronavirus/metabolism , Computational Biology/methods , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Envelope Proteins/immunology , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/immunology , Epitope Mapping , Gene Expression Regulation, Viral , Humans , Models, Molecular , One Health , Pandemics , Phylogeny , Protein Conformation , Sequence Alignment , Sequence Analysis, Protein
12.
Biomed Res Int ; 2020: 2683286, 2020.
Article in English | MEDLINE | ID: covidwho-400795

ABSTRACT

Background: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. Method: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.


Subject(s)
Betacoronavirus/immunology , Computational Biology/methods , Coronavirus Infections/immunology , Epitopes/immunology , Pneumonia, Viral/immunology , Vaccines, Subunit/immunology , Viral Proteins/immunology , Viral Vaccines/immunology , Amino Acid Sequence , Coronavirus Infections/prevention & control , Epitopes/chemistry , Epitopes, T-Lymphocyte/immunology , Evolution, Molecular , HLA Antigens/immunology , Humans , Models, Molecular , Pandemics , Software , Viral Proteins/chemistry
13.
Microbes Infect ; 22(4-5): 182-187, 2020.
Article in English | MEDLINE | ID: covidwho-346567

ABSTRACT

Envelope protein of coronaviruses is a structural protein existing in both monomeric and homo-pentameric form. It has been related to a multitude of roles including virus infection, replication, dissemination and immune response stimulation. In the present study, we employed an immunoinformatic approach to investigate the major immunogenic domains of the SARS-CoV-2 envelope protein and map them among the homologue proteins of coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Also, when not available, we predicted the envelope protein structural folding and mapped SARS-CoV-2 epitopes. Envelope sequences alignment provides evidence of high sequence homology for some of the investigated virus specimens; while the structural mapping of epitopes resulted in the interesting maintenance of the structural folding and epitope sequence localization also in the envelope proteins scoring a lower alignment score. In line with the One-Health approach, our evidences provide a molecular structural rationale for a potential role of taxonomically related coronaviruses in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.


Subject(s)
Betacoronavirus/metabolism , Computational Biology/methods , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Envelope Proteins/immunology , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/immunology , Epitope Mapping , Gene Expression Regulation, Viral , Humans , Models, Molecular , One Health , Pandemics , Phylogeny , Protein Conformation , Sequence Alignment , Sequence Analysis, Protein
14.
Cell Syst ; 10(5): 379-380, 2020 05 20.
Article in English | MEDLINE | ID: covidwho-324678

ABSTRACT

We asked speakers from the Annual International Conference on Research in Computational Molecular Biology (RECOMB) about how computational biology as a discipline is being affected by COVID-19 and how the expertise of their community can help in the global response to the pandemic.


Subject(s)
Computational Biology/methods , Congresses as Topic , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Humans , Interdisciplinary Communication , Pandemics , Software
15.
Immunobiology ; 225(3): 151955, 2020 05.
Article in English | MEDLINE | ID: covidwho-309013

ABSTRACT

SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Viral Proteins/chemistry , Viral Vaccines/biosynthesis , Amino Acid Sequence , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Computational Biology/methods , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Disease Progression , Epitopes/chemistry , Epitopes/immunology , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , HLA Antigens/genetics , HLA Antigens/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunogenicity, Vaccine , Molecular Docking Simulation , Plasmids/chemistry , Plasmids/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Conformation , Reverse Genetics/methods , Sequence Alignment , Vaccines, Subunit , Viral Proteins/genetics , Viral Proteins/immunology
16.
J Med Virol ; 92(6): 618-631, 2020 06.
Article in English | MEDLINE | ID: covidwho-141989

ABSTRACT

Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Toll-Like Receptor 5/chemistry , Viral Vaccines/chemistry , Amino Acid Sequence , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Binding Sites , Computational Biology/methods , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/chemistry , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Molecular Docking Simulation , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Tertiary , SARS Virus/genetics , SARS Virus/immunology , SARS Virus/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Toll-Like Receptor 5/genetics , Toll-Like Receptor 5/immunology , Vaccines, Subunit , Viral Vaccines/immunology
17.
J Med Virol ; 92(6): 693-697, 2020 06.
Article in English | MEDLINE | ID: covidwho-8443

ABSTRACT

An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an important polymerase that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS-CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π-cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study.


Subject(s)
Antiviral Agents/chemistry , Betacoronavirus/drug effects , Biflavonoids/chemistry , Catechin/chemistry , Drugs, Chinese Herbal/chemistry , RNA Replicase/chemistry , Viral Proteins/chemistry , Amino Acid Sequence , Antiviral Agents/pharmacology , Betacoronavirus/enzymology , Betacoronavirus/genetics , Biflavonoids/pharmacology , Catalytic Domain , Catechin/pharmacology , Computational Biology/methods , Drugs, Chinese Herbal/pharmacology , Gene Expression , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/enzymology , Middle East Respiratory Syndrome Coronavirus/genetics , Molecular Docking Simulation , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , RNA Replicase/antagonists & inhibitors , RNA Replicase/genetics , RNA Replicase/metabolism , SARS Virus/drug effects , SARS Virus/enzymology , SARS Virus/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Thermodynamics , Viral Proteins/antagonists & inhibitors , Viral Proteins/genetics , Viral Proteins/metabolism
18.
J Med Virol ; 92(6): 688-692, 2020 06.
Article in English | MEDLINE | ID: covidwho-8355

ABSTRACT

The city of Wuhan, Hubei province, China, was the origin of a severe pneumonia outbreak in December 2019, attributed to a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), causing a total of 2761 deaths and 81109 cases (25 February 2020). SARS-CoV-2 belongs to genus Betacoronavirus, subgenus Sarbecovirus. The polyprotein 1ab (pp1ab) remains unstudied thoroughly since it is similar to other sarbecoviruses. In this short communication, we performed phylogenetic-structural sequence analysis of pp1ab protein of SARS-CoV-2. The analysis showed that the viral pp1ab has not changed in most isolates throughout the outbreak time, but interestingly a deletion of 8 aa in the virulence factor nonstructural protein 1 was found in a virus isolated from a Japanese patient that did not display critical symptoms. While comparing pp1ab protein with other betacoronaviruses, we found a 42 amino acid signature that is only present in SARS-CoV-2 (AS-SCoV2). Members from clade 2 of sarbecoviruses have traces of this signature. The AS-SCoV2 located in the acidic-domain of papain-like protein of SARS-CoV-2 and bat-SL-CoV-RatG13 guided us to suggest that the novel 2019 coronavirus probably emerged by genetic drift from bat-SL-CoV-RaTG13. The implication of this amino acid signature in papain-like protein structure arrangement and function is something worth to be explored.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , SARS Virus/genetics , Viral Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Betacoronavirus/classification , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , Chiroptera/microbiology , Computational Biology/methods , Coronavirus Infections/transmission , Coronavirus Infections/virology , Evolution, Molecular , Gene Expression , Humans , Papain/genetics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS Virus/classification , SARS Virus/pathogenicity , Sequence Alignment , Sequence Homology, Amino Acid , Viral Nonstructural Proteins/genetics
19.
Life Sci ; 248: 117477, 2020 May 01.
Article in English | MEDLINE | ID: covidwho-2799

ABSTRACT

AIMS: A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp). MATERIALS AND METHODS: In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin. KEY FINDINGS: The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease. SIGNIFICANCE: The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/chemistry , Betacoronavirus/enzymology , Coronavirus Infections/drug therapy , Guanosine Monophosphate/analogs & derivatives , Pneumonia, Viral/drug therapy , RNA Replicase/antagonists & inhibitors , Ribavirin/chemistry , Sofosbuvir/chemistry , Viral Proteins/antagonists & inhibitors , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/chemistry , Alanine/metabolism , Alphacoronavirus/enzymology , Alphacoronavirus/genetics , Amino Acid Sequence , Antiviral Agents/metabolism , Betacoronavirus/genetics , Catalytic Domain , Computational Biology/methods , Coronavirus Infections/virology , Drug Repositioning/methods , Guanosine Monophosphate/chemistry , Guanosine Monophosphate/metabolism , Guanosine Triphosphate/chemistry , Guanosine Triphosphate/metabolism , Humans , Molecular Docking Simulation , Pneumonia, Viral/virology , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , RNA Replicase/chemistry , RNA Replicase/metabolism , Ribavirin/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Sofosbuvir/metabolism , Thermodynamics , Uridine Triphosphate/chemistry , Uridine Triphosphate/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism
20.
J Med Virol ; 92(6): 618-631, 2020 06.
Article in English | MEDLINE | ID: covidwho-2731

ABSTRACT

Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Epitopes, B-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/chemistry , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Toll-Like Receptor 5/chemistry , Viral Vaccines/chemistry , Amino Acid Sequence , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Binding Sites , Computational Biology/methods , Coronavirus Infections/immunology , Coronavirus Infections/virology , Epitopes/chemistry , Epitopes/genetics , Epitopes/immunology , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/chemistry , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Molecular Docking Simulation , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Tertiary , SARS Virus/genetics , SARS Virus/immunology , SARS Virus/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Toll-Like Receptor 5/genetics , Toll-Like Receptor 5/immunology , Vaccines, Subunit , Viral Vaccines/immunology
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