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1.
Medicine (Baltimore) ; 100(51): e27112, 2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1595314

ABSTRACT

BACKGROUND: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. METHODS: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. RESULTS: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. CONCLUSION: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the "cytokine storm," and anti-viral entry into cells.

2.
J Med Internet Res ; 23(2): e25682, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1574621

ABSTRACT

BACKGROUND: Since the outbreak of COVID-19, the development of dashboards as dynamic, visual tools for communicating COVID-19 data has surged worldwide. Dashboards can inform decision-making and support behavior change. To do so, they must be actionable. The features that constitute an actionable dashboard in the context of the COVID-19 pandemic have not been rigorously assessed. OBJECTIVE: The aim of this study is to explore the characteristics of public web-based COVID-19 dashboards by assessing their purpose and users ("why"), content and data ("what"), and analyses and displays ("how" they communicate COVID-19 data), and ultimately to appraise the common features of highly actionable dashboards. METHODS: We conducted a descriptive assessment and scoring using nominal group technique with an international panel of experts (n=17) on a global sample of COVID-19 dashboards in July 2020. The sequence of steps included multimethod sampling of dashboards; development and piloting of an assessment tool; data extraction and an initial round of actionability scoring; a workshop based on a preliminary analysis of the results; and reconsideration of actionability scores followed by joint determination of common features of highly actionable dashboards. We used descriptive statistics and thematic analysis to explore the findings by research question. RESULTS: A total of 158 dashboards from 53 countries were assessed. Dashboards were predominately developed by government authorities (100/158, 63.0%) and were national (93/158, 58.9%) in scope. We found that only 20 of the 158 dashboards (12.7%) stated both their primary purpose and intended audience. Nearly all dashboards reported epidemiological indicators (155/158, 98.1%), followed by health system management indicators (85/158, 53.8%), whereas indicators on social and economic impact and behavioral insights were the least reported (7/158, 4.4% and 2/158, 1.3%, respectively). Approximately a quarter of the dashboards (39/158, 24.7%) did not report their data sources. The dashboards predominately reported time trends and disaggregated data by two geographic levels and by age and sex. The dashboards used an average of 2.2 types of displays (SD 0.86); these were mostly graphs and maps, followed by tables. To support data interpretation, color-coding was common (93/158, 89.4%), although only one-fifth of the dashboards (31/158, 19.6%) included text explaining the quality and meaning of the data. In total, 20/158 dashboards (12.7%) were appraised as highly actionable, and seven common features were identified between them. Actionable COVID-19 dashboards (1) know their audience and information needs; (2) manage the type, volume, and flow of displayed information; (3) report data sources and methods clearly; (4) link time trends to policy decisions; (5) provide data that are "close to home"; (6) break down the population into relevant subgroups; and (7) use storytelling and visual cues. CONCLUSIONS: COVID-19 dashboards are diverse in the why, what, and how by which they communicate insights on the pandemic and support data-driven decision-making. To leverage their full potential, dashboard developers should consider adopting the seven actionability features identified.


Subject(s)
COVID-19 , Data Display , Information Dissemination , Internet , Adult , Computer Graphics , Disease Outbreaks , Female , Humans , Information Storage and Retrieval , Male , Pandemics , SARS-CoV-2 , Young Adult
3.
Security and Communication Networks ; 2021, 2021.
Article in English | ProQuest Central | ID: covidwho-1556792

ABSTRACT

Novel coronavirus spreads fast and has a huge impact on the whole world. In light of the spread of novel coronaviruses, we develop one big data prediction model of novel coronavirus epidemic in the context of intelligent medical treatment, taking into account all factors of infection and death and implementing emerging technologies, such as the Internet of Things (IoT) and machine learning. Based on the different application characteristics of various machine learning algorithms in the medical field, we propose one artificial intelligence prediction model based on random forest. Considering the loose coupling between the data preparation stage and the model training stage, such as data collection and data cleaning in the early stage, we adopt the IoT platform technology to integrate the data collection, data cleaning, machine learning training model, and front- and back-end frameworks to ensure the tight coupling of each module. To validate the proposed prediction model, we perform the evaluation work. In addition, the performance of the prediction model is analyzed to ensure the information accuracy of the prediction platform.

4.
Preprint in English | EuropePMC | ID: ppcovidwho-294885

ABSTRACT

The novel coronavirus disease, named COVID-19, emerged in China in December 2019, and has rapidly spread around the world. It is clearly urgent to fight COVID-19 at global scale. The development of methods for identifying drug uses based on phenotypic data can improve the efficiency of drug development. However, there are still many difficulties in identifying drug applications based on cell picture data. This work reported one state-of-the-art machine learning method to identify drug uses based on the cell image features of 1024 drugs generated in the LINCS program. Because the multi-dimensional features of the image are affected by non-experimental factors, the characteristics of similar drugs vary greatly, and the current sample number is not enough to use deep learning and other methods are used for learning optimization. As a consequence, this study is based on the supervised ITML algorithm to convert the characteristics of drugs. The results show that the characteristics of ITML conversion are more conducive to the recognition of drug functions. The analysis of feature conversion shows that different features play important roles in identifying different drug functions. For the current COVID-19, Chloroquine and Hydroxychloroquine achieve antiviral effects by inhibiting endocytosis, etc., and were classified to the same community. And Clomiphene in the same community inibited the entry of Ebola Virus, indicated a similar MoAs that could be reflected by cell image.

5.
Front Microbiol ; 12: 755599, 2021.
Article in English | MEDLINE | ID: covidwho-1482024

ABSTRACT

Although plateau pikas are the keystone species in the plateau ecosystem of the Qinghai Province of China, little is known about their role in the evolution and transmission of viral pathogens, especially coronaviruses. Here, we describe the characterization and evolution of a novel alphacoronavirus, termed plateau pika coronavirus (PPCoV) P83, which has a prevalence of 4.5% in plateau pika fecal samples. In addition to classical gene order, the complete viral genome contains a unique nonstructural protein (NS2), several variable transcription regulatory sequences and a highly divergent spike protein. Phylogenetic analysis indicates that the newly discovered PPCoV falls into the genus Alphacoronavirus and is most closely related to rodent alphacoronaviruses. The co-speciation analysis shows that the phylogenetic trees of the alphacoronaviruses and their hosts are not always matched, suggesting inter-species transmission is common in alphacoronaviruses. And, PPCoV origin was estimated by molecular clock based on membrane and RNA-dependent RNA polymerase encoding genes, respectively, which revealed an apparent discrepancy with that of co-speciation analysis. PPCoV was detected mainly in intestinal samples, indicating a potential enteric tropism for the virus. Overall, this study extends the host range of alphacoronaviruses to a new order (Lagomorpha), indicating that plateau pikas may be the natural reservoir of PPCoV and play an important and long-term role in alphacoronavirus evolution.

6.
Theor Appl Genet ; 134(9): 3083-3109, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1453686

ABSTRACT

KEY MESSAGE: Based on the large-scale integration of meta-QTL and Genome-Wide  Association Study, 76 high-confidence MQTL regions and 237 candidate genes that affected wheat yield and yield-related traits were discovered. Improving yield and yield-related traits are key goals in wheat breeding program. The integration of accumulated wheat genetic resources provides an opportunity to uncover important genomic regions and candidate genes that affect wheat yield. Here, a comprehensive meta-QTL analysis was conducted on 2230 QTL of yield-related traits obtained from 119 QTL studies. These QTL were refined into 145 meta-QTL (MQTL), and 89 MQTL were verified by GWAS with different natural populations. The average confidence interval (CI) of these MQTL was 2.92 times less than that of the initial QTL. Furthermore, 76 core MQTL regions with a physical distance less than 25 Mb were detected. Based on the homology analysis and expression patterns, 237 candidate genes in the MQTL involved in photoperiod response, grain development, multiple plant growth regulator pathways, carbon and nitrogen metabolism and spike and flower organ development were determined. A novel candidate gene TaKAO-4A was confirmed to be significantly associated with grain size, and a CAPS marker was developed based on its dominant haplotype. In summary, this study clarified a method based on the integration of meta-QTL, GWAS and homology comparison to reveal the genomic regions and candidate genes that affect important yield-related traits in wheat. This work will help to lay a foundation for the identification, transfer and aggregation of these important QTL or candidate genes in wheat high-yield breeding.


Subject(s)
Chromosomes, Plant/genetics , Edible Grain/genetics , Genome, Plant , Genome-Wide Association Study , Plant Proteins/metabolism , Quantitative Trait Loci , Triticum/genetics , Chromosome Mapping/methods , Edible Grain/growth & development , Gene Expression Regulation, Plant , Phenotype , Plant Breeding , Plant Proteins/genetics , Triticum/growth & development
7.
Nat Commun ; 12(1): 502, 2021 01 21.
Article in English | MEDLINE | ID: covidwho-1387327

ABSTRACT

The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein's central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates. In cells, N forms condensates that recruit the stress granule protein G3BP1, highlighting a potential role for N in G3BP1 sequestration and stress granule inhibition. The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate. These findings support a model in which phase separation of the SARS-CoV-2 N protein contributes both to suppression of the G3BP1-dependent host immune response and to packaging genomic RNA during virion assembly.


Subject(s)
COVID-19/virology , Coronavirus Nucleocapsid Proteins/metabolism , RNA, Viral/metabolism , SARS-CoV-2/metabolism , Viral Matrix Proteins/metabolism , COVID-19/genetics , COVID-19/metabolism , Cell Membrane/virology , Coronavirus Nucleocapsid Proteins/chemistry , Coronavirus Nucleocapsid Proteins/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , Humans , Phosphoproteins/chemistry , Phosphoproteins/genetics , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , Protein Binding , Protein Domains , RNA Helicases/genetics , RNA Helicases/metabolism , RNA Recognition Motif Proteins/genetics , RNA Recognition Motif Proteins/metabolism , RNA, Viral/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/genetics
8.
Virol Sin ; 36(3): 402-411, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1372824

ABSTRACT

Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning. One type of those commonly emerging and re-emerging pathogens are coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2). Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission. However, little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province, where has the greatest biodiversity among the world's high-altitude regions. Here, from the next-generation sequencing data, we obtained a known beta-coronavirus (beta-CoV) genome and a novel delta-coronavirus (delta-CoV) genome from faecal samples of 29 marmots, 50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture, Qinghai Province, China in July 2019. According to the phylogenetic analysis, the beta-CoV shared high nucleotide identity with Coronavirus HKU24. Although the novel delta-CoV (MtCoV) was closely related to Sparrow deltacoronavirus ISU42824, the protein spike of the novel delta-CoV showed highest amino acid identity to Sparrow coronavirus HKU17 (73.1%). Interestingly, our results identified a novel host (Montifringilla taczanowskii) for the novel delta-CoV and the potential cross-species transmission. The most recent common ancestor (tMRCA) of MtCoVs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago. Thus, this study increases our understanding of the genetic diversity of beta-CoVs and delta-CoVs, and also provides a new perspective of the coronavirus hosts.


Subject(s)
Animals, Wild/virology , Coronavirus/isolation & purification , Phylogeny , Animals , Birds/virology , China , Coronavirus/classification , Marmota/virology , Rats/virology , Tibet
9.
Information Sciences ; 2021.
Article in English | ScienceDirect | ID: covidwho-1370549

ABSTRACT

Using cross-asset return data in global financial markets, we propose a novel empirical framework to identify the causal structure of the asset risk spillover network. The joint return distribution of the global financial system can be characterized using a directed acyclic graph approach. However, since assets tend to be highly correlated during market turbulence, when adopting a nodewise penalized regression approach for neighborhood estimation, parameter estimates will receive large standard errors, and edges cannot be reliably estimated. In this work, we propose a two-stage approach for directed acyclic graph skeleton estimation for highly correlated variables. In the first stage, a variable screening ensemble is incorporated into the sparse partial least squares regression method to both reduce the size of the active variables set and impose an adaptive penalization on the weight vectors. In the second stage, a modified PC algorithm based on Gram-Schmidt orthogonalization is applied to remove the false positive edges. Simulation studies are conducted to demonstrate the effectiveness of the proposed method. Finally, we apply our method to analyze the asset risk spillover channels for international financial assets during the COVID-19 pandemic.

10.
Front Immunol ; 12: 719037, 2021.
Article in English | MEDLINE | ID: covidwho-1354866

ABSTRACT

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is the most severe public health event of the twenty-first century. While effective vaccines against SARS-CoV-2 have been developed, there remains an urgent need for diagnostics to quickly and accurately detect infections. Antigen tests, particularly those that detect the abundant SARS-CoV-2 Nucleocapsid protein, are a proven method for detecting active SARS-CoV-2 infections. Here we report high-resolution crystal structures of three llama-derived single-domain antibodies that bind the SARS-CoV-2 Nucleocapsid protein with high affinity. Each antibody recognizes a specific folded domain of the protein, with two antibodies recognizing the N-terminal RNA binding domain and one recognizing the C-terminal dimerization domain. The two antibodies that recognize the RNA binding domain affect both RNA binding affinity and RNA-mediated phase separation of the Nucleocapsid protein. All three antibodies recognize highly conserved surfaces on the Nucleocapsid protein, suggesting that they could be used to develop affordable diagnostic tests to detect all circulating SARS-CoV-2 variants.


Subject(s)
COVID-19 Serological Testing/methods , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus Nucleocapsid Proteins/ultrastructure , Single-Domain Antibodies/immunology , Single-Domain Antibodies/ultrastructure , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Crystallography, X-Ray , Humans , Protein Domains , SARS-CoV-2/immunology
12.
J Biosaf Biosecur ; 3(1): 58-65, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1284238

ABSTRACT

The re-emerging outbreak of COVID-19 in Beijing, China, in the summer of 2020 originated from a SARS-CoV-2-infested wholesale food supermarket. We postulated that the Xinfadi market outbreak has links with food-trade activities. Our Susceptible to the disease, Infectious, and Recovered coupled Agent Based Modelling (SIR-ABM) analysis for studying the diffusion of SARS-CoV-2 particles suggested that the trade-distancing strategy effectively reduces the reproduction number (R0). The retail shop closure strategy reduced the number of visitors to the market by nearly half. In addition, the buy-local policy option reduced the infection by more than 70% in total. Therefore, retail closures and buy-local policies could serve as significantly effective strategies that have the potential to reduce the size of the outbreak and prevent probable outbreaks in the future.

13.
J Biosaf Biosecur ; 3(1): 35-40, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1240455

ABSTRACT

Introduction: The significance of asymptomatic or pre-asymptomatic individuals in driving the COVID-19 epidemic in China or other countries remains uncertain. Method: We collected and analyzed all the epidemiologic and virological diagnostic details of the infected individuals released by public health authorities and reiterated every episode of outbreak on a timeline. All individuals associated with the five outbreaks had tested positive for SARS-CoV-2 infection. Results: In this study, all five COVID-19 outbreaks reported in China since October 2020 were analyzed. The Kashgar outbreak in Xinjiang province came into light for the first time on October 22, 2020. However, it was initiated before October 11, 2020, by a local asymptomatic import and export worker, who was infected at the working place. Subsequently, his wife caught the infection, which led to 430 more infections reported in the outbreak. The Beijing outbreak with 41 cases was noticed for the first time on December 22, 2020. However, our analysis revealed that it was initiated by an asymptomatic individual from Indonesia on December 10, 2020. The Shenyang outbreak, with 38 cases, noticed for the first time on December 23, 2020, was initiated by a pre-symptomatic individual from South Korea on December 13, 2020. Conclusion: The asymptomatic or pre-symptomatic individuals during the asymptomatic period were unsuspectingly infected by SARS-CoV-2, and unintentionally transmitted the virus to a large number of people. These findings suggest that early detection of asymptomatic or pre-symptomatic individuals is of critical importance in preventing future outbreaks or epidemics.

14.
J Immunol ; 206(11): 2527-2535, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1227097

ABSTRACT

The T cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine development. The present study was undertaken to determine the T cell epitopes in the spike (S) protein of SARS-CoV-2 that dominate the T cell responses in SARS-CoV-2-infected patients. PBMCs from rhesus macaques vaccinated with a DNA vaccine encoding the full-length S protein were isolated, and an ELISPOT assay was used to identify the recognized T cell epitopes among a total of 158 18-mer and 10-aa-overlapping peptides spanning the full-length S protein. Six multipeptide-based epitopes located in the S1 region, with four of the six located in the receptor-binding domain, were defined as the most frequently recognized epitopes in macaques. The conservation of the epitopes across species was also verified, and peptide mixtures for T cell response detection were established. Six newly defined T cell epitopes were found in the current study, which may provide a novel potential target for T cell response detection and the diagnosis and vaccine design of SARS-CoV-2 based on multipeptide subunit-based epitopes.


Subject(s)
Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Macaca mulatta
15.
Vaccine ; 39(20): 2746-2754, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1174522

ABSTRACT

BACKGROUND: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. METHOD: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated. RESULTS: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine. INTERPRETATION: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. TRIAL REGISTRATION: CTR20200943 and NCT04412538.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines , Adolescent , Adult , Antibodies, Viral , China , Double-Blind Method , Humans , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Young Adult
16.
Int J Endocrinol ; 2021: 6616069, 2021.
Article in English | MEDLINE | ID: covidwho-1140370

ABSTRACT

COVID-19 is a kind of pneumonia with new coronavirus infection, and the risk of death in COVID-19 patients with diabetes is four times higher than that in healthy people. It is unclear whether there is a difference in chest CT images between type 2 diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) COVID-19 patients. The aim of this study was to investigate the differences in chest CT images between T2DM and NDM patients with COVID-19 based on a quantitative method of artificial intelligence. A total of 62 patients with COVID-19 pneumonia were retrospectively enrolled and divided into group A (T2DM COVID-19 pneumonia group, n = 15) and group B (NDM COVID-19 pneumonia group, n = 47). The clinical and laboratory examination information of the two groups was collected. Quantitative features (volume of consolidation shadows and ground glass shadows, proportion of consolidation shadow (or ground glass shadow) to lobe volume, total volume, total proportion, and number) of chest spiral CT images were extracted using Dr. Wise @Pneumonia software. The results showed that among the 26 CT image features, the total volume and proportion of bilateral pulmonary consolidation shadow in group A were larger than those in group B (P=0.031 and 0.019, respectively); there was no significant difference in the total volume and proportion of bilateral pulmonary ground glass density shadow between the two groups (P > 0.05). In group A, the blood glucose level was correlated with the volume of consolidation shadow and the proportion of consolidation shadow to right middle lobe volume, and higher than those patients in group B. In conclusion, the inflammatory exudation in the lung of COVID-19 patients with diabetes is more serious than that of patients without diabetes based on the quantitative method of artificial intelligence. Moreover, the blood glucose level is positively correlated with pulmonary inflammatory exudation in COVID-19 patients.

17.
Emerg Microbes Infect ; 10(1): 342-355, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1069193

ABSTRACT

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Vaccines, Subunit/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , DNA/immunology , HEK293 Cells , Humans , Lymphocyte Count , Macaca mulatta , Mice , Mice, Inbred C57BL , Plasmids/genetics , Rabbits , Recombinant Proteins/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , T-Lymphocytes/immunology
18.
Front Public Health ; 8: 604870, 2020.
Article in English | MEDLINE | ID: covidwho-1063368

ABSTRACT

Objective: To clarify the correlation between temperature and the COVID-19 pandemic in Hubei. Methods: We collected daily newly confirmed COVID-19 cases and daily temperature for six cities in Hubei Province, assessed their correlations, and established regression models. Results: For temperatures ranging from -3.9 to 16.5°C, daily newly confirmed cases were positively correlated with the maximum temperature ~0-4 days prior or the minimum temperature ~11-14 days prior to the diagnosis in almost all selected cities. An increase in the maximum temperature 4 days prior by 1°C was associated with an increase in the daily newly confirmed cases (~129) in Wuhan. The influence of temperature on the daily newly confirmed cases in Wuhan was much more significant than in other cities. Conclusion: Government departments in areas where temperatures range between -3.9 and 16.5°C and rise gradually must take more active measures to address the COVID-19 pandemic.


Subject(s)
Air , COVID-19 , Climate , Temperature , COVID-19/epidemiology , COVID-19/transmission , China , Cities , Humans
19.
J Ethnopharmacol ; 273: 113871, 2021 Jun 12.
Article in English | MEDLINE | ID: covidwho-1042531

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan". AIM OF THE STUDY: To elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19. METHODS: This study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results. RESULTS: We concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 µg crude drugs/mL (2.405 µg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity. CONCLUSION: RDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/chemistry , Antiviral Agents/toxicity , Cell Line, Transformed , Chlorocebus aethiops , Computational Biology , Coronavirus 3C Proteases/metabolism , Coronavirus Papain-Like Proteases/metabolism , Cytokines/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/toxicity , Humans , Medicine, Chinese Traditional/methods , Molecular Docking Simulation , Protein Array Analysis , SARS-CoV-2/drug effects , Signal Transduction/drug effects , Vero Cells
20.
Preprint | SciFinder | ID: ppcovidwho-4913

ABSTRACT

A review. The prevention and control strategy of the outpatient drug dispensing center of medical institutions during the outbreak of COVID-19 was established, providing reference for the first-line dispensing departments of outpatient dispensing pharmacies, outpatient pharmacies and emergency pharmacies of medical institutions in China to actively deal with the epidemic situation. Method: Improve epidemic prevention and control organizations, establish emergency plans, implement personnel protection measures at three risk levels and management of key disinfection rules in five regions, summarize the responsibilities of each department for ensuring supply and carrying out pharmaceutical care. Result: During the epidemic period, the prevention and control measures of the personnel of the outpatient service deployment center were scientific and effective, and all departments operated in an orderly manner to guarantee the basis and emergency drug supply for fever outpatient service and outpatient and emergency treatment, and to provide high-quality and efficient pharmaceutical care for patients. In conclusion, it is very important to introduce the management strategy of "focusing on prevention and control with one hand and providing services with the other" in a timely manner. Through scientific prevention and control, so as to give full play to the important responsibilities of front line pharmaceutical personnel.

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