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SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    The Impact of Intervention to Routine Surveillance of Natural Focal Diseases During the Outbreak of COVID-19 MESHD in Jiangsu Province, China

    Authors: Jianli Hu; Xiaoqing Cheng; Li Luo; Zeyu Zhao; Nan Zhang; Mikah Ngwanguong Hannah; Jia Rui; Shengnan Lin; Xingchun Liu; Yuanzhao Zhu; Yao Wang; Meng Yang; Jingwen Xu; Tianlong Yang; Weikang Liu; Peihua Li; Bin Deng; Zhuoyang Li; Chan Liu; Jiefeng Huang; Cangjun Bao; Tianmu Chen

    doi:10.21203/rs.3.rs-135563/v1 Date: 2020-12-24 Source: ResearchSquare

    Background: With the strength intervention of China, the outbreak of Severe Acute Respiratory Syndrome-Coronavirus MESHD 2 (SARS-CoV-2) had a great control effect. The measures may influence the development and progression of others infectious diseases MESHD.Method: The data of daily coronavirus virus disease MESHD 2019 ( COVID-19 MESHD) confirmed cases from January 3, 2020 to April 30, 2020 and natural focal disease cases from January, 2005 to April, 2020 were collected from Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial CDC). We describe and compare the data of natural focal diseases from January to April, 2020 with the same months from 2015 to 2019 in the four aspects: trend of incidence, regional, age and sex distribution. Nonparametric tests were used to analyzed to the difference between the duration from onset of illness to date of diagnosis of natural focal diseases and the same period of the previous year. Results: The incidence of malaria MESHD in February (0.9 per 10,000,000 people), March (0.3 per 10,000,000 people) and April (0.1 per 10,000,000 people) 2020 less than the lower limit for range of February (1.6-4.5 per 10,000,000 people), March (0.8-3.3 per 10,000,000 people) and April (1.0-2.9 per 10,000,000 people) from 2015 to 2019 respectively. The incidence of brucellosis MESHD in February was 0.9 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.6-4.5 per 10,000,000 people). The incidence of hemorrhagic fever MESHD ( HF MESHD) in March was 1.0 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.4-2.6 per 10,000,000 people). However, the incidence of Severe Fever MESHD with Thrombocytopenia Syndrome MESHD ( SEFT MESHD) in March was 0.3 (per 10,000,000 people), higher than the upper limit for the range from 2015 to 2019 (0.0-0.1 per 10,000,000 people). Furthermore, we respectively observed the incidence with various degree of reduction in male, 20-60 years old and both rural and urban areas. Conclusions: In Jiangsu province, the incidence of natural focal diseases decreased during the outbreak of COVID-19 MESHD in 2020, especially malaria MESHD, HF MESHD and SEFT. The impact of interventions were felt most by male individuals within the age group of 20-50 years. The interventions for COVID-19 MESHD may control the epidemics of natural focal diseases.

    Evaluating ten commercially-available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) method.

    Authors: Laurent Dortet; Jean-Baptiste Ronat; Christelle Vauloup-Fellous; Céline Langendorf; David-Alexis Mendels; Cécile Emeraud; Saoussen Oueslati; Delphine Girlich; Anthony Chauvin; Ali Afdjei; Sandrine Bernabeu; Samuel Le Pape; Rim Kallala; Alice Rochard; Celine Verstuyft; Nicolas Fortineau; Anne-Marie Roque-Afonso; Thierry Naas

    doi:10.1101/2020.09.10.20192260 Date: 2020-09-11 Source: medRxiv

    Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV-2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N=254) were retrieved from pre-COVID periods from patients with other coronavirus infections MESHD (N=11), positive rheumatoid MESHD factors (N=3), IgG/ IgM hyperglobulinemia MESHD (N=9), malaria MESHD (n=5), or no documented viral infection MESHD (N=226). All samples were tested using rapid lateral flow immunoassays (LFIA) from ten manufacturers. Only four tests achieved [≥]98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%-92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities' thresholds for SARS-CoV-2 serological tests ([≥]90% sensitivity + [≥]98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians to use them with more confidence, could help determine the general population's immunological status, and may diagnose some patients with false-negative RT-PCR results.

    Diagnostics and spread of SARS-CoV-2 in Western Africa: An observational laboratory-based study from Benin

    Authors: Anges Yadouleton; Anna-Lena Sander; Andres Moreira-Soto; Carine Tchibozo; Gildas Hounkanrin; Yvette Badou; Carlo Fischer; Nina Krause; Petas Akogbeto; Edmilson F. de Oliveira Filho; Anges Dossou; Sebastian Bruenink; Melchior AIssi; Mamoudou Harouna Djingarey; Benjamin Hounkpatin; Michael Nagel; Jan Felix Drexler

    doi:10.1101/2020.06.29.20140749 Date: 2020-07-08 Source: medRxiv

    Information on severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) spread in Africa is limited by fragile 2 surveillance systems and insufficient diagnostic capacity. 3 We assessed the coronavirus disease-19 MESHD ( COVID-19 MESHD)-related diagnostic workload in Benin, Western Africa, 4 characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19 MESHD, used those together with public data to 5 estimate SARS-CoV-2 transmission dynamics in a Bayesian framework, validated a widely used diagnostic dual target 6 RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 MESHD 7 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction. 8 We found a 15-fold increase in the monthly laboratory workload due to COVID-19 MESHD. Genomic surveillance showed 9 introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 estimate of 10 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests 11 were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available 12 SARS-CoV-2 ELISAs showed up to 25% false-positive results depending on antigen and antibody types, likely due 13 to unspecific antibody responses elicited by acute malaria MESHD according to lack of SARS-CoV-2-specific neutralizing 14 antibody responses and relatively higher parasitemia MESHD in those sera. 15 We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of 16 genome-based surveillance in resource-limited settings. Sero-epidemiological studies needed to assess SARS-CoV-2 17 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges 18 demand continuous support of national and supranational African stakeholders.

    Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box’s Molecules

    Authors: Cleidy Osorio-Mogollon; Gustavo E. Olivos-Ramirez; Kewin Otazu; Manuel E. Chenet-Zuta; Georcki Ropon-Palacios; Ihosvany Camps; Gabriel M. Jimenez-Avalo; Eduardo Apari-Cossio; Natalia E. Torres-Moreira; Reyna G. Cardenas-Cardenas

    doi:10.26434/chemrxiv.12501791.v1 Date: 2020-06-19 Source: ChemRxiv

    The world is currently facing a pandemic caused by the new 2019 coronavirus disease MESHD ( COVID-19 MESHD), caused by SARS-CoV-2. Among the fundamental processes of this virus are viral transcription and replication. They allow the synthesisof genetic material and the consequent multiplication of the virus to infect other cells or organisms. These are performed by a multi-subunit machinery of various nonstructural proteins ( nsp HGNC); among which the RNA-dependent RNApolymerase ( RdRp PROTEIN or nsp12) is the most important, and, at the same time, conserved among coronaviruses. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for drugsearch, like virtual screening and molecular docking. The region considered for virtual screening has three important amino acids for protein catalysis: T680 (located in Motif A), N691 and D623 (located in Motif B), where a grid box was located. In turn, applying the concept of drug repositioning isconsidered as a quick response in the treatment of sudden outbreaks of diseases. Here, we used the Pathogen Box, a database of chemical compounds analyzed for the treatment against malaria MESHD, which were filtered under the criteria of selecting those that do not present any violation of Lipinski'sRule of Five. At the same time, the Remdesivir, Beclabuvir and Sofosbuvir drug, previously used in in silico and clinical studies for inhibition of nsp12, were used as positive controls. The results showed a Top10 potential target inhibitors, with binding energy higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with -7.53 kcal/mol, present interactions with the three important residues of the nsp12 catalytic site. These proposed ligands would be used for subsequent validation by molecular dynamics, where they can beconsidered as drugs for the development of effective treatments against this new pandemic.

    Comparative analyses revealed reduced spread of COVID-19 MESHD in malaria endemic countries

    Authors: Azhar Muneer; Kiran Kumari; Manish Tripathi; Rupesh Srivastava; Asif Mohmmed; Sumit Rathore

    doi:10.1101/2020.05.11.20097923 Date: 2020-05-14 Source: medRxiv

    In late 2019, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection MESHD started in Hubei province of China and now it has spread like a wildfire in almost all parts of the world except some. WHO named the disease caused by SARS-CoV-2 as COVID-19 MESHD ( CoronaVirus Disease MESHD-2019). It is very intriguing to see a mild trend of infection in some countries which could be attributed to mitigation efforts, lockdown strategies, health infrastructure, demographics and cultural habits. However, the lower rate of infection and death MESHD rates in mostly developing countries, which are not placed at higher levels in terms of healthcare facilities, is a very surprising observation. To address this issue, we hypothesize that this lower rate of infection is majorly been observed in countries which have a higher transmission/prevalence of protozoan parasite borne disease MESHD, malaria MESHD. We compared the COVID-19 MESHD spread and malaria MESHD endemicity of 108 countries which have shown at least 200 cases of COVID-19 MESHD till 18th April 2020. We found that the number of COVID-19 MESHD cases per million population correlates negatively with the malaria MESHD endemicity of respective countries. The malaria MESHD free countries not only have higher density of COVID-19 MESHD infections but also the higher case fatality rates as compared to highly malaria MESHD endemic countries. We also postulate that this phenomenon is due to natural immune response against malaria infection MESHD, which is providing a heterologous protection against the virus. Unfortunately, there is no licensed vaccine against SARS-CoV-2 yet, but this information will be helpful in design of future strategies against fast spreading COVID-19 MESHD disease.

    Using Supervised Machine Learning and Empirical Bayesian Kriging to reveal Correlates and Patterns of COVID-19 MESHD Disease outbreak in sub-Saharan Africa: Exploratory Data Analysis

    Authors: Amobi Andrew Onovo; Akinyemi Atobatele; Abiye Kalaiwo; Christopher Obanubi; Ezekiel James; Pamela Gado; Gertrude Odezugo; Doreen Magaji; Dolapo Ogundehin; Michele Russell

    doi:10.1101/2020.04.27.20082057 Date: 2020-05-02 Source: medRxiv

    Introduction: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is an emerging infectious disease MESHD that was first reported in Wuhan, China, and has subsequently spread worldwide. Knowledge of coronavirus-related risk factors can help countries build more systematic and successful responses to COVID-19 MESHD disease outbreak. Here we used Supervised Machine Learning and Empirical Bayesian Kriging MESHD (EBK) techniques to reveal correlates and patterns of COVID-19 MESHD Disease outbreak in sub-Saharan Africa (SSA). Methods: We analyzed time series aggregate data compiled by Johns Hopkins University on the outbreak of COVID-19 MESHD disease across SSA. COVID-19 MESHD data was merged with additional data on socio-demographic and health indicator survey data for 39 of SSA 48 countries that reported confirmed cases and deaths from coronavirus between February 28, 2020 through March 26, 2020. We used supervised machine learning algorithm, Lasso for variable selection and statistical inference. EBK was used to also create a raster estimating the spatial distribution of COVID-19 MESHD disease outbreak. Results: The lasso Cross-fit partialing out predictive model ascertained seven variables significantly associated with the risk of coronavirus infection MESHD (i.e. new HIV infections MESHD among pediatric, adolescent, and middle-aged adult PLHIV, time (days), pneumococcal MESHD conjugate-based vaccine, incidence of malaria MESHD and diarrhea MESHD treatment). Our study indicates, the doubling time in new coronavirus cases was 3 days. The steady three-day decrease in coronavirus outbreak rate of change (ROC) from 37% on March 23, 2020 to 23% on March 26, 2020 indicates the positive impact of countries' steps to stymie the outbreak. The interpolated maps show that coronavirus is rising every day and appears to be severely confined in South Africa. In the West African region (i.e. Burkina Faso, Ghana, Senegal, CotedIviore, Cameroon, and Nigeria), we predict that new cases and deaths MESHD from the virus are most likely to increase. Interpretation: Integrated and efficiently delivered interventions to reduce HIV MESHD, pneumonia MESHD, malaria MESHD and diarrhea MESHD, are essential to accelerating global health efforts. Scaling up screening and increasing COVID-19 MESHD testing capacity across SSA countries can help provide better understanding on how the pandemic is progressing and possibly ensure a sustained decline in the ROC of coronavirus outbreak. Funding: Authors were wholly responsible for the costs of data collation and analysis.

    In Vitro Virucidal Effect of Intranasally Delivered Chlorpheniramine Maleate Compound Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

    Authors: Gustavo Ferrer; Jonna Westover

    doi:10.21203/rs.3.rs-25854/v1 Date: 2020-04-28 Source: ResearchSquare

     Background. The initial global outbreak of the novel coronavirus disease 2019 MESHD (COVID-2019) pandemic, responsible for the severe acute respiratory syndrome MESHD 2 (SARS-CoV-2), was first reported in Wuhan, China, at the end of December 2019. COVID-19 MESHD shares similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) MESHD, and it behaves similarly to influenza with a high intranasal viral load. The genome sequence of COVID-19 MESHD opened the opportunity for multiple in vitro and clinical trials, but we still do not have a clear path to treatment. Chlorpheniramine is a safe and effective antihistamine with potent antiviral activity against various strains of influenza A/B, thus suggesting that CPM has broad antiviral activity. We tested the virucidal potential of chlorpheniramine maleate (CPM) in a nasal spray composition currently in development as an anti- allergy MESHD medication.Methods. The virucidal activity of chlorpheniramine maleate was tested using viral stock of SARS-CoV-2, USA-WA1/2020 strain in Vero 76 infected cells. The end-point titer (CCID50) values were calculated with the Reed-Muench (1948) equation. Three independent replicates of each sample were tested, and the average and standard deviation were calculated. Results were compared with untreated controls by one-way ANOVA with Dunnett’s multiple comparison test in GraphPad Prism (version 8) software. Results. After 25-minutes of contact time, the nasal spray reduced the levels of the virus from 4.2 to 1.7 log10 CCID50 per 0.1 mL, a statistically significant reduction of 2.5 log10 CCID50.Conclusions. This study demonstrates the strong virucidal effect against SARS-CoV-2 of a nasal spray containing chlorpheniramine maleate. Given that CPM has broad antiviral effects against influenza, virucidal effect against SARS-CoV-2, and coadjuvant effects with hydroxychloroquine in treating multidrug-resistant malaria MESHD with minimal side effects. We propose two further studies: a randomized placebo-controlled study of intranasally delivered chlorpheniramine in patients with mild to moderate SARS-CoV-2, and a second study aiming to determine the potential antiviral and adjuvant effects of CPM plus hydroxychloroquine, versus chloroquine alone, in hospitalized patients with SARS-CoV-2.   

    Myths and Facts: Chloroquine May Be A Potential Supportive/Therapeutic Drug in COVID-19 MESHD Treatment

    Authors: Muhammad Kashif; Muhammad Aamir; Sadia Minhas; Romeeza Tahir; Shah Jahan; Nadeem Afzal

    id:10.20944/preprints202004.0341.v1 Date: 2020-04-19 Source: Preprints.org

    Quinine and its less toxic derivatives have served humanity for decades as potent antimalarial drugs. Emergence of drug resistance has narrowed the usage of these drugs in malaria MESHD prevention and treatment. Fortunately, these drugs have roles in the treatment of other diseases as well including rheumatic disorders MESHD and viral infections MESHD. Quinine derivatives have proven antiviral effects, especially against human immunodeficiency virus (HIV), Zika virus MESHD (ZiKV), herpes simplex virus (HSV), Ebola virus MESHD and dengue virus (DENV). The prophylactic and therapeutic role of Chloroquine/hydroxychroquine has become a topic of interest after the recent outbreak of novel Corona virus-19 (nCoV-19). This virus is also named severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) and WHO has officially named this disease as Corona virus disease MESHD 2019 ( COVID-19 MESHD). This lethal virus has affected almost 186 countries of the world till to date just in a period of four months of its outbreak. No approved antiviral drug is existed for the treatment of COVID-19 MESHD. Therefore, this review is focused on potential prophylactic and therapeutic role of chloroquine/hydroxychlroquine for COVID-19 MESHD.

    Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19 MESHD

    Authors: Meehyun Ko; So Young Chang; Soo Young Byun; Inhee Choi; David Shum; Ji-Young Min; Marc P. Windisch

    doi:10.1101/2020.02.25.965582 Date: 2020-03-02 Source: bioRxiv

    In 2015, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV MESHD) reached the Republic of Korea through nosocomial transmission and was the largest epidemic outside of the Arabian Peninsula. To date, despite various strategies to identify CoV interventions, only limited therapeutic options are available. To address these unmet medical needs, we used a South Korean MERS-CoV clinical isolate and screened 5,406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactive molecules, for their activity against the isolate. The primary assay confirmed 221 hits by dose-response curve analysis and identified 54 hits with a therapeutic index (TI) greater than 6. Time-of-addition studies with 12 FDA-approved drugs demonstrated that 8 and 4 therapeutics act on the early and late stages of the viral life cycle, respectively. Among the drugs were e.g., three cardiotonic agents (ouabain, digitoxin, digoxin) with a TI greater than 100, an anti- malaria MESHD drug (atovaquone; TI >34), an inhalable corticosteroid (ciclesonide; TI >6), etc. Together, our results identify potential therapeutic options for treating MERS-CoV infections MESHD and could provide a basis for agents against a wider range of coronavirus-related illnesses, including the currently emerging Coronavirus Disease MESHD Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) outbreak.

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