Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 67
Filter
1.
Sci Rep ; 12(1): 5709, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1778628

ABSTRACT

This article presents a method for trend clustering from tweets about coronavirus disease (COVID-19) to help us objectively review the past and make decisions about future countermeasures. We aim to avoid detecting usual trends based on seasonal events while detecting essential trends caused by the influence of COVID-19. To this aim, we regard daily changes in the frequencies of each word in tweets as time series signals and define time series signals with single peaks as target trends. To successfully cluster the target trends, we propose graphical lasso-guided iterative principal component analysis (GLIPCA). GLIPCA enables us to remove trends with indirect correlations generated by other essential trends. Moreover, GLIPCA overcomes the difficulty in the quantitative evaluation of the accuracy of trend clustering. Thus, GLIPCA's parameters are easier to determine than those of other clustering methods. We conducted experiments using Japanese tweets about COVID-19 from March 8, 2020, to May 7, 2020. The results show that GLIPCA successfully distinguished trends before and after the declaration of a state of emergency on April 7, 2020. In addition, the results reveal the international argument about whether the Tokyo 2020 Summer Olympics should be held. The results suggest the tremendous social impact of the words and actions of Japanese celebrities. Furthermore, the results suggest that people's attention moved from worry and fear of an unknown novel pneumonia to the need for medical care and a new lifestyle as well as the scientific characteristics of COVID-19.


Subject(s)
COVID-19 , Social Media , COVID-19/epidemiology , Cluster Analysis , Humans , Principal Component Analysis , SARS-CoV-2
2.
Sci Rep ; 12(1): 4150, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1735291

ABSTRACT

Models of animals that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can usefully evaluate the efficacy of vaccines and therapeutics. In this study, we demonstrate that infection with the SARS-CoV-2 B.1.351 variant (TY8-612 strain) induces bodyweight loss and inflammatory cytokine/chemokine production in wild-type laboratory mice (BALB/c and C57BL/6 J mice). Furthermore, compared to their counterparts, BALB/c mice had a higher viral load in their lungs and worse symptoms. Importantly, infecting aged BALB/c mice (older than 6 months) with the TY8-612 strain elicited a massive and sustained production of multiple pro-inflammatory cytokines/chemokines and led to universal mortality. These results indicated that the SARS-CoV-2 B.1.351 variant-infected mice exhibited symptoms ranging from mild to fatal depending on their strain and age. Our data provide insights into the pathogenesis of SARS-CoV-2 and may be useful in developing prophylactics and therapeutics.


Subject(s)
COVID-19/pathology , SARS-CoV-2/physiology , Aging , Animals , COVID-19/mortality , COVID-19/virology , Chemokines/metabolism , Cytokines/metabolism , Disease Models, Animal , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Principal Component Analysis , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Viral Load
3.
Sci Rep ; 12(1): 4040, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1735284

ABSTRACT

To provide novel data on surfactant levels in adult COVID-19 patients, we collected bronchoalveolar lavage fluid less than 72 h after intubation and used Fourier Transform Infrared Spectroscopy to measure levels of dipalmitoylphosphatidylcholine (DPPC). A total of eleven COVID-19 patients with moderate-to-severe ARDS (CARDS) and 15 healthy controls were included. CARDS patients had lower DPPC levels than healthy controls. Moreover, a principal component analysis was able to separate patient groups into distinguishable subgroups. Our findings indicate markedly impaired pulmonary surfactant levels in COVID-19 patients, justifying further studies and clinical trials of exogenous surfactant.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , COVID-19/pathology , Pulmonary Surfactants/analysis , 1,2-Dipalmitoylphosphatidylcholine/analysis , Adult , Aged , COVID-19/virology , Case-Control Studies , Female , Humans , Male , Middle Aged , Principal Component Analysis , Pulmonary Surfactants/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spectrophotometry, Infrared/methods
4.
Genes (Basel) ; 13(2)2022 02 14.
Article in English | MEDLINE | ID: covidwho-1686686

ABSTRACT

The use of high-throughput small RNA sequencing is well established as a technique to unveil the miRNAs in various tissues. The miRNA profiles are different between infected and non-infected tissues. We compare the SARS-CoV-2 positive and SARS-CoV-2 negative RNA samples extracted from human nasopharynx tissue samples to show different miRNA profiles. We explored differentially expressed miRNAs in response to SARS-CoV-2 in the RNA extracted from nasopharynx tissues of 10 SARS-CoV-2-positive and 10 SARS-CoV-2-negative patients. miRNAs were identified by small RNA sequencing, and the expression levels of selected miRNAs were validated by real-time RT-PCR. We identified 943 conserved miRNAs, likely generated through posttranscriptional modifications. The identified miRNAs were expressed in both RNA groups, NegS and PosS: miR-148a, miR-21, miR-34c, miR-34b, and miR-342. The most differentially expressed miRNA was miR-21, which is likely closely linked to the presence of SARS-CoV-2 in nasopharynx tissues. Our results contribute to further understanding the role of miRNAs in SARS-CoV-2 pathogenesis, which may be crucial for understanding disease symptom development in humans.


Subject(s)
MicroRNAs/metabolism , Nasopharynx/metabolism , SARS-CoV-2/physiology , COVID-19/pathology , COVID-19/virology , Down-Regulation , High-Throughput Nucleotide Sequencing , Humans , MicroRNAs/chemistry , Nasopharynx/virology , Principal Component Analysis , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA , Transcriptome , Up-Regulation
5.
Cell ; 185(5): 916-938.e58, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1654147

ABSTRACT

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/pathology , Proteome/analysis , Adult , Blood Proteins/metabolism , COVID-19/blood , COVID-19/virology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Female , Humans , Influenza, Human/blood , Influenza, Human/pathology , Lymphocytes/immunology , Lymphocytes/metabolism , Machine Learning , Male , Middle Aged , Mitogen-Activated Protein Kinase 14/genetics , Mitogen-Activated Protein Kinase 14/metabolism , Monocytes/immunology , Monocytes/metabolism , Principal Component Analysis , SARS-CoV-2/isolation & purification , Sepsis/blood , Sepsis/pathology , Severity of Illness Index , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism
6.
PLoS One ; 16(12): e0261776, 2021.
Article in English | MEDLINE | ID: covidwho-1631646

ABSTRACT

The Coronavirus Disease 2019 has resulted in a transition from physical education to online learning, leading to a collapse of the established educational order and a wisdom test for the education governance system. As a country seriously affected by the pandemic, the health of the Indian higher education system urgently requires assessment to achieve sustainable development and maximize educational externalities. This research systematically proposes a health assessment model from four perspectives, including educational volume, efficiency, equality, and sustainability, by employing the Technique for Order Preference by Similarity to an Ideal Solution Model, Principal Component Analysis, DEA-Tobit Model, and Augmented Solow Model. Empirical results demonstrate that India has high efficiency and an absolute health score in the higher education system through multiple comparisons between India and the other selected countries while having certain deficiencies in equality and sustainability. Additionally, single-target and multiple-target path are simultaneously proposed to enhance the Indian current education system. The multiple-target approach of the India-China-Japan-Europe-USA process is more feasible to achieve sustainable development, which would improve the overall health score from .351 to .716. This finding also reveals that the changes are relatively complex and would take 91.5 years considering the relationship between economic growth rates and crucial indicators. Four targeted policies are suggested for each catching-up period, including expanding and increasing the social funding sources, striving for government expenditure support to improve infrastructures, imposing gender equality in education, and accelerating the construction of high-quality teachers.


Subject(s)
COVID-19/epidemiology , Education, Distance/methods , Educational Status , Models, Theoretical , Pandemics , SARS-CoV-2 , Sustainable Development , COVID-19/virology , China/epidemiology , Europe/epidemiology , Humans , India/epidemiology , Japan/epidemiology , Principal Component Analysis/methods , United States/epidemiology
7.
Phys Chem Chem Phys ; 24(3): 1743-1759, 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1606147

ABSTRACT

The outbreak caused by SARS-CoV-2 has received extensive worldwide attention. As the main protease (Mpro) in SARS-CoV-2 has no human homologues, it is feasible to reduce the possibility of targeting the host protein by accidental drugs. Thus, Mpro has been an attractive target of efficient drug design for anti-SARS-CoV-2 treatment. In this work, multiple replica molecular dynamics (MRMD) simulations, principal component analysis (PCA), free energy landscapes (FELs), and the molecular mechanics-generalized Born surface area (MM-GBSA) method were integrated together to decipher the binding mechanism of four inhibitors masitinib, O6K, FJC and GQU to Mpro. The results indicate that the binding of four inhibitors clearly affects the structural flexibility and internal dynamics of Mpro along with dihedral angle changes of key residues. The analysis of FELs unveils that the stability in the relative orientation and geometric position of inhibitors to Mpro is favorable for inhibitor binding. Residue-based free energy decomposition reveals that the inhibitor-Mpro interaction networks involving hydrogen bonding interactions and hydrophobic interactions provide significant information for the design of potent inhibitors against Mpro. The hot spot residues including H41, M49, F140, N142, G143, C145, H163, H164, M165, E166 and Q189 identified by computational alanine scanning are considered as reliable targets of clinically available inhibitors inhibiting the activities of Mpro.


Subject(s)
Antiviral Agents/chemistry , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Proline/chemistry , SARS-CoV-2/drug effects , Viral Protease Inhibitors/chemistry , Antiviral Agents/pharmacology , Drug Design , Humans , Molecular Dynamics Simulation , Principal Component Analysis , Proline/pharmacology , Protein Binding , Protein Conformation , Structure-Activity Relationship , Thermodynamics , Viral Protease Inhibitors/pharmacology
8.
PLoS One ; 16(12): e0260899, 2021.
Article in English | MEDLINE | ID: covidwho-1546972

ABSTRACT

The COVID-19 is one of the worst pandemics in modern history. We applied principal component analysis (PCA) to the daily time series of the COVID-19 death cases and confirmed cases for the top 25 countries from April of 2020 to February of 2021. We calculated the eigenvalues and eigenvectors of the cross-correlation matrix of the changes in daily accumulated data over monthly time windows. The largest eigenvalue describes the overall evolution dynamics of the COVID-19 and indicates that evolution was faster in April of 2020 than in any other period. By using the first two PC coefficients, we can identify the group dynamics of the COVID-19 evolution. We observed groups under critical states in the loading plot and found that American and European countries are represented by strong clusters in the loading plot. The first PC plays an important role and the correlations (C1) between the normalized logarithmic changes in deaths or confirmed cases and the first PCs may be used as indicators of different phases of the COVID-19. By varying C1 over time, we identified different phases of the COVID-19 in the analyzed countries over the target time period.


Subject(s)
COVID-19/epidemiology , Americas/epidemiology , COVID-19/mortality , Europe/epidemiology , Global Health/statistics & numerical data , Humans , Principal Component Analysis
9.
Inflamm Res ; 71(1): 131-140, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1544398

ABSTRACT

OBJECTIVES: The role of B cells in COVID-19, beyond the production of specific antibodies against SARS-CoV-2, is still not well understood. Here, we describe the novel landscape of circulating double-negative (DN) CD27- IgD- B cells in COVID-19 patients, representing a group of atypical and neglected subpopulations of this cell lineage. METHODS: Using multiparametric flow cytometry, we determined DN B cell subset amounts from 91 COVID-19 patients, correlated those with cytokines, clinical and laboratory parameters, and segregated them by principal components analysis. RESULTS: We detected significant increments in the DN2 and DN3 B cell subsets, while we found a relevant decrease in the DN1 B cell subpopulation, according to disease severity and patient outcomes. These DN cell numbers also appeared to correlate with pro- or anti-inflammatory signatures, respectively, and contributed to the segregation of the patients into disease severity groups. CONCLUSION: This study provides insights into DN B cell subsets' potential role in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/immunology , Immunoglobulin D/blood , SARS-CoV-2 , Tumor Necrosis Factor Receptor Superfamily, Member 7/blood , Adult , Aged , Aged, 80 and over , B-Lymphocytes/cytology , COVID-19/diagnosis , COVID-19/virology , Cell Lineage , Computational Biology , Disease Progression , Female , Humans , Male , Middle Aged , Principal Component Analysis , Prognosis , Respiration, Artificial , Severity of Illness Index , Young Adult
10.
J Med Virol ; 93(12): 6595-6604, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544310

ABSTRACT

As a kind of human betacoronavirus, SARS-CoV-2 has endangered globally public health. As of January 2021, the virus had resulted in 2,209,195 deaths. By studying the evolution trend and characteristics of 265 SARS-CoV-2 strains in the United States from January to March, it is found that the strains can be divided into six clades, USA clade-1, USA clade-2, USA clade-3, USA clade-4, USA clade-5, and USA clade-6, in which US clade-1 may be the most ancestral clade, USA clade-2 is an interim clade of USA clade-1 and USA clade-3, the other three clades have similar codon usage pattern, while USA clade-6 is the newest and most adaptable clade. Mismatch analysis and protein alignment showed that the evolution of the clades arises from some special mutations in viral proteins, which may help the strain to invade, replicate, transcribe and so on. Compared with previous research and classifications, we suggest that clade O in GISAID should not be an independent clade and Wuhan-Hu-1 (EPI_ISL_402125) should not be an ancestral reference sequence. Our study decoded the evolutionary dynamic of SARS-CoV-2 in the early stage from the United States, which give some clues to infer the current evolution trend of SARS-CoV-2 and study the function of viral mutational protein.


Subject(s)
Evolution, Molecular , SARS-CoV-2/genetics , Bayes Theorem , COVID-19/virology , Humans , Mutation/genetics , Phylogeny , Principal Component Analysis , Sequence Alignment , United States/epidemiology
11.
Sci Rep ; 11(1): 22855, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1532103

ABSTRACT

Policymakers commonly employ non-pharmaceutical interventions to reduce the scale and severity of pandemics. Of non-pharmaceutical interventions, physical distancing policies-designed to reduce person-to-person pathogenic spread - have risen to recent prominence. In particular, stay-at-home policies of the sort widely implemented around the globe in response to the COVID-19 pandemic have proven to be markedly effective at slowing pandemic growth. However, such blunt policy instruments, while effective, produce numerous unintended consequences, including potentially dramatic reductions in economic productivity. In this study, we develop methods to investigate the potential to simultaneously contain pandemic spread while also minimizing economic disruptions. We do so by incorporating both occupational and contact network information contained within an urban environment, information that is commonly excluded from typical pandemic control policy design. The results of our methods suggest that large gains in both economic productivity and pandemic control might be had by the incorporation and consideration of simple-to-measure characteristics of the occupational contact network. We find evidence that more sophisticated, and more privacy invasive, measures of this network do not drastically increase performance.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control/economics , Communicable Disease Control/methods , Contact Tracing/economics , Contact Tracing/methods , Disease Transmission, Infectious/prevention & control , Humans , Occupations/classification , Pandemics , Physical Distancing , Policy , Principal Component Analysis , Quarantine/economics , Quarantine/methods , Quarantine/trends , SARS-CoV-2/pathogenicity
12.
Elife ; 102021 11 23.
Article in English | MEDLINE | ID: covidwho-1529013

ABSTRACT

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/blood , Coronavirus/immunology , Cross Reactions/immunology , Healthy Volunteers , Humans , Immunoglobulin G/immunology , Macaca , Middle East Respiratory Syndrome Coronavirus/immunology , Principal Component Analysis , Protein Domains/immunology , Serum/immunology , Serum/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Tetanus Toxoid/immunology , /immunology
13.
Sci Rep ; 11(1): 20866, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1479816

ABSTRACT

A causal relationship between plasma ceramide concentration and respiratory distress symptoms in COVID-19 patients is inferred. In this study, plasma samples of 52 individuals infected with COVID-19 were utilized in a lipidomic analysis. Lipids belonging to the ceramide class exhibited a 400-fold increase in total plasma concentration in infected patients. Further analysis led to the demonstration of concentration dependency for severe COVID-19 respiratory symptoms in a subclass of ceramides. The subclasses Cer(d18:0/24:1), Cer(d18:1/24:1), and Cer(d18:1/22:0) were shown to be increased by 48-, 40-, and 33-fold, respectively, in infected plasma samples and to 116-, 91- and 50-fold, respectively, in plasma samples with respiratory distress. Hence, monitoring plasma ceramide concentration, can be a valuable tool for measuring effects of therapies on COVID-19 respiratory distress patients.


Subject(s)
COVID-19/blood , COVID-19/complications , Ceramides/blood , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/complications , Adult , Aged , Aged, 80 and over , Chromatography, Liquid , Drug Design , Female , Humans , Ions , Lipids/chemistry , Male , Metabolomics , Middle Aged , Principal Component Analysis , Software , Tandem Mass Spectrometry , Virus Diseases , Young Adult
14.
Int J Mol Sci ; 22(20)2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1470893

ABSTRACT

SputnikV is a vaccine against SARS-CoV-2 developed by the Gamaleya National Research Centre for Epidemiology and Microbiology. The vaccine has been shown to induce both humoral and cellular immune responses, yet the mechanisms remain largely unknown. Forty SputnikV vaccinated individuals were included in this study which aimed to demonstrate the location of immunogenic domains of the SARS-CoV-2 S protein using an overlapping peptide library. Additionally, cytokines in the serum of vaccinated and convalescent COVID-19 patients were analyzed. We have found antibodies from both vaccinated and convalescent sera bind to immunogenic regions located in multiple domains of SARS-CoV-2 S protein, including Receptor Binding Domain (RBD), N-terminal Domain (NTD), Fusion Protein (FP) and Heptad Repeats (HRs). Interestingly, many peptides were recognized by immunized and convalescent serum antibodies and correspond to conserved regions in circulating variants of SARS-CoV-2. This breadth of reactivity was still evident 90 days after the first dose of the vaccine, showing that the vaccine has induced a prolonged response. As evidenced by the activation of T cells, cellular immunity strongly suggests the high potency of the SputnikV vaccine against SARS-CoV-2 infection.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunity, Cellular , Immunity, Humoral , Adult , Amino Acid Sequence , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cytokines/metabolism , Female , Humans , Male , Peptides/chemistry , Peptides/immunology , Principal Component Analysis , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccination
15.
Comput Math Methods Med ; 2021: 2203636, 2021.
Article in English | MEDLINE | ID: covidwho-1443668

ABSTRACT

Coronavirus disease 2019 (COVID-19) arising from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic since its first report in December 2019. So far, SARS-CoV-2 nucleic acid detection has been deemed as the golden standard of COVID-19 diagnosis. However, this detection method often leads to false negatives, thus triggering missed COVID-19 diagnosis. Therefore, it is urgent to find new biomarkers to increase the accuracy of COVID-19 diagnosis. To explore new biomarkers of COVID-19 in this study, expression profiles were firstly accessed from the GEO database. On this basis, 500 feature genes were screened by the minimum-redundancy maximum-relevancy (mRMR) feature selection method. Afterwards, the incremental feature selection (IFS) method was used to choose a classifier with the best performance from different feature gene-based support vector machine (SVM) classifiers. The corresponding 66 feature genes were set as the optimal feature genes. Lastly, the optimal feature genes were subjected to GO functional enrichment analysis, principal component analysis (PCA), and protein-protein interaction (PPI) network analysis. All in all, it was posited that the 66 feature genes could effectively classify positive and negative COVID-19 and work as new biomarkers of the disease.


Subject(s)
Biomarkers/metabolism , COVID-19/genetics , COVID-19/metabolism , Algorithms , COVID-19 Testing , Computational Biology , False Negative Reactions , False Positive Reactions , Gene Expression Profiling , Humans , Machine Learning , Models, Statistical , Principal Component Analysis , Protein Interaction Mapping , Research Design , Sensitivity and Specificity
16.
Virus Res ; 305: 198579, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433887

ABSTRACT

The SARS-CoV2 mediated Covid-19 pandemic has impacted humankind at an unprecedented scale. While substantial research efforts have focused towards understanding the mechanisms of viral infection and developing vaccines/ therapeutics, factors affecting the susceptibility to SARS-CoV2 infection and manifestation of Covid-19 remain less explored. Given that the Human Leukocyte Antigen (HLA) system is known to vary among ethnic populations, it is likely to affect the recognition of the virus, and in turn, the susceptibility to Covid-19. To understand this, we used bioinformatic tools to probe all SARS-CoV2 peptides which could elicit T-cell response in humans. We also tried to answer the intriguing question of whether these potential epitopes were equally immunogenic across ethnicities, by studying the distribution of HLA alleles among different populations and their share of cognate epitopes. Results indicate that the immune recognition potential of SARS-CoV2 epitopes tend to vary between different ethnic groups. While the South Asians are likely to recognize higher number of CD8-specific epitopes, Europeans are likely to identify higher number of CD4-specific epitopes. We also hypothesize and provide clues that the newer mutations in SARS-CoV2 are unlikely to alter the T-cell mediated immunogenic responses among the studied ethnic populations. The work presented herein is expected to bolster our understanding of the pandemic, by providing insights into differential immunological response of ethnic populations to the virus as well as by gaging the possible effects of mutations in SARS-CoV2 on efficacy of potential epitope-based vaccines through evaluating ∼40,000 viral genomes.


Subject(s)
COVID-19/immunology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Genome, Viral , HLA Antigens/immunology , SARS-CoV-2/immunology , Africa/epidemiology , Alleles , Amino Acid Sequence , Asia/epidemiology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/pathology , Computational Biology/methods , Disease Susceptibility , Epitopes, B-Lymphocyte/classification , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/classification , Epitopes, T-Lymphocyte/genetics , Europe/epidemiology , HLA Antigens/classification , HLA Antigens/genetics , Humans , Middle East/epidemiology , Oceania/epidemiology , Principal Component Analysis , RNA, Viral/genetics , RNA, Viral/immunology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity
17.
J Chem Theory Comput ; 17(10): 6483-6490, 2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1404872

ABSTRACT

SARS-CoV-2 that caused COVID-19 has spread since the end of 2019. Its major effects resulted in over four million deaths around the whole world by August 2021. Therefore, understanding virulence mechanisms is important to prevent future outbreaks and for COVID-19 drug development. The envelope (E) protein is an important structural protein, affecting virus assembly and budding. The E protein pentamer is a viroporin, serving as an ion transferring channel in cells. In this work, we applied molecular dynamic simulations and topological and electrostatic analyses to study the effects of palmitoylation on the E protein pentamer. The results indicate that the cation transferring direction is more from the lumen to the cytosol. The structure of the palmitoylated E protein pentamer is more stable while the loss of palmitoylation caused the pore radius to reduce and even collapse. The electrostatic forces on the two sides of the palmitoylated E protein pentamer are more beneficial to attract cations in the lumen and to release cations into the cytosol. The results indicate the importance of palmitoylation, which can help the drug design for the treatment of COVID-19.


Subject(s)
Coronavirus Envelope Proteins/chemistry , Lipoylation , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cations/chemistry , Computational Biology , Cytosol/chemistry , Drug Design , Humans , Models, Molecular , Molecular Dynamics Simulation , Molecular Structure , Principal Component Analysis , Protons , Static Electricity
18.
PLoS One ; 16(5): e0247626, 2021.
Article in English | MEDLINE | ID: covidwho-1388902

ABSTRACT

SARS-CoV-2 infection in minks has become a serious problem, as the virus may mutate and reinfect humans; some countries have decided to cull minks. Here, the virus sequencing data in minks were analysed and compared to those of human-virus. Although the mink-virus maintained the characteristics of human-virus, some variants rapidly mutated, adapting to minks. Some mink-derived variants infected humans, which accounted for 40% of the total SARS-CoV-2 cases in the Netherlands. These variants appear to be less lethal and infective compared to those in humans. Variants that have mutated further among minks were not found in humans. Such mink-viruses might be suitable for vaccination for humans, such as in the case of the smallpox virus, which is less infective and toxic to humans.


Subject(s)
COVID-19/pathology , Mink/virology , RNA, Viral/chemistry , SARS-CoV-2/genetics , Animals , COVID-19/epidemiology , COVID-19/veterinary , COVID-19/virology , Humans , Mutation , Netherlands/epidemiology , Principal Component Analysis , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Sequence Analysis, RNA
19.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1388433

ABSTRACT

The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Animals , Cryoelectron Microscopy , Enzyme-Linked Immunosorbent Assay , Humans , Image Processing, Computer-Assisted , Ligands , Mice , Mice, Inbred BALB C , Mutation , Peptides/chemistry , Polysaccharides , Principal Component Analysis , Protein Binding , Protein Domains
20.
Sci Rep ; 11(1): 6621, 2021 03 23.
Article in English | MEDLINE | ID: covidwho-1387468

ABSTRACT

The human bronchial epithelium is the first line of defense against atmospheric particles, pollutants, and respiratory pathogens such as the novel SARS-CoV-2. The epithelial cells form a tight barrier and secrete proteins that are major components of the mucosal immune response. Functional in vitro models of the human lung are essential for screening the epithelial response and assessing the toxicity and barrier crossing of drugs, inhaled particles, and pollutants. However, there is a lack of models to investigate the effect of chronic exposure without resorting to animal testing. Here, we developed a 3D model of the human bronchial epithelium using Calu-3 cell line and demonstrated its viability and functionality for 21 days without subculturing. We investigated the effect of reduced Fetal Bovine Serum supplementation in the basal medium and defined the minimal supplementation needed to maintain a functional epithelium, so that the amount of exogenous serum proteins could be reduced during drug testing. The long-term evolution of the epithelial cell secretome was fully characterized by quantitative mass spectrometry in two preclinical models using Calu-3 or primary NHBE cells. 408 common secreted proteins were identified while significant differences in protein abundance were observed with time, suggesting that 7-10 days are necessary to establish a mature secretome in the Calu-3 model. The associated Reactome pathways highlight the role of the secreted proteins in the immune response of the bronchial epithelium. We suggest this preclinical 3D model can be used to evaluate the long-term toxicity of drugs or particles on the human bronchial epithelium, and subsequently to investigate their effect on the epithelial cell secretions.


Subject(s)
Epithelial Cells/metabolism , Proteome/analysis , Proteomics/methods , Angiotensin-Converting Enzyme 2/metabolism , Bronchi/cytology , COVID-19/pathology , COVID-19/virology , Cell Culture Techniques , Cell Line , Culture Media/chemistry , Epithelial Cells/cytology , Humans , Mass Spectrometry , Models, Biological , Principal Component Analysis , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
SELECTION OF CITATIONS
SEARCH DETAIL