Corpus overview


MeSH Disease

Human Phenotype

Fever (13)

Cough (12)

Hypertension (12)

Pneumonia (12)

Fatigue (6)


    displaying 1 - 10 records in total 85
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    Small-Molecule In Vitro Inhibitors of the Coronavirus Spike - ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

    Authors: Damir Bojadzic; Oscar Alcazar; Jinshui Chen; Peter Buchwald; Georges Schmartz; Tobias Fehlmann; Nicholas Schaum; Davis P Lee; Kruti Calcuttawala; Ryan T Vest; David Gate; Daniela Berdnik; M. Windy McNerney; Divya Channappa; Inma Cobos; Nicole Ludwig; Walter J. Schulz-Schaeffer; Andreas Keller; Tony Wyss-Coray; Marco Soriani; Antonella Folgori; Jonathan K Ball; Stefano Colloca; Bertrand Degos; Louise-Laure Mariani; Christophe Bouche; Nathalie Dzierzynski; Bruno Oquendo; Flora Ketz; An-Hung Nguyen; Aurelie Kas; Jean-Yves Delattre; Jean-Christophe Corvol

    doi:10.1101/2020.10.22.351056 Date: 2020-10-22 Source: bioRxiv

    Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and ACE2, which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than with antibodies SERO, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable / less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound-library that is focused on the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA SERO-type assays (IC50s of 0.2-3.0 M); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs identified here bind SARS-CoV-2-S and not ACE2. Selected promising compounds inhibited the entry of a SARS-CoV-2-S expressing pseudovirus into ACE2-expressing cells in concentration-dependent manner with low micromolar IC50s (6-30 M). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for coronavirus attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases MESHD caused by coronaviruses in general and COVID-19 in particular.

    Drug Repurposing for COVID-19 via Knowledge Graph Completion

    Authors: Rui Zhang; Dimitar Hristovski; Dalton Schutte; Andrej Kastrin; Marcelo Fiszman; Halil Kilicoglu

    id:2010.09600v1 Date: 2020-10-19 Source: arXiv

    Objective: To discover candidate drugs to repurpose for COVID-19 using literature-derived knowledge and knowledge graph completion methods. Methods: We propose a novel, integrative, and neural network-based literature-based discovery (LBD) approach to identify drug candidates from both PubMed and COVID-19-focused research literature. Our approach relies on semantic triples extracted using SemRep (via SemMedDB). We identified an informative subset of semantic triples using filtering rules and an accuracy classifier developed on a BERT variant, and used this subset to construct a knowledge graph. Five SOTA, neural knowledge graph completion algorithms were used to predict drug repurposing candidates. The models were trained and assessed using a time slicing approach and the predicted drugs were compared with a list of drugs reported in the literature and evaluated in clinical trials. These models were complemented by a discovery pattern-based approach. Results: Accuracy classifier based on PubMedBERT achieved the best performance SERO (F1= 0.854) in classifying semantic predications. Among five knowledge graph completion models, TransE outperformed others (MR = 0.923, Hits@1=0.417). Some known drugs linked to COVID-19 in the literature were identified, as well as some candidate drugs that have not yet been studied. Discovery patterns enabled generation of plausible hypotheses regarding the relationships between the candidate drugs and COVID-19. Among them, five highly ranked and novel drugs (paclitaxel, SB 203580, alpha 2-antiplasmin, pyrrolidine dithiocarbamate, and butylated hydroxytoluene) with their mechanistic explanations were further discussed. Conclusion: We show that an LBD approach can be feasible for discovering drug candidates for COVID-19, and for generating mechanistic explanations. Our approach can be generalized to other diseases MESHD as well as to other clinical questions.

    On Modeling of COVID-19 for the Indian Subcontinent using Polynomial and Supervised Learning Regression MESHD

    Authors: Dishita Neve; Honey Patel; Harsh S Dhiman; Victoria Acquaye; Alfred D. Dai-Kosi; Alejandro J Krolewiecki; Juan P Aparicio; Haifeng Wang; Dejing Dou; Pete Bond; Paul Anthony McAry; Sharad Bhagat; Itti Munshi; Swapneil Parikh; Sachee Agrawal; Chandrakant Pawar; Mala Kaneria; Smita Mahale; Jayanthi Shastri; Vainav Patel; Paul Dark; Alexander Mathioudakis; Kathryn Gray; Graham Lord; Timothy Felton; Chris Brightling; Ling-Pei Ho; - NIHR Respiratory TRC; - CIRCO; Karen Piper Hanley; Angela Simpson; John R Grainger; Tracy Hussell; Elizabeth R Mann

    doi:10.1101/2020.10.14.20212563 Date: 2020-10-16 Source: medRxiv

    COVID-19, a recently declared pandemic by WHO has taken the world by storm causing catastrophic damage MESHD to human life. The novel cornonavirus disease MESHD was first incepted in the Wuhan city of China on 31st December 2019. The symptoms include fever HP fever MESHD, cough HP cough MESHD, fatigue HP fatigue MESHD, shortness of breath MESHD or breathing difficulties, and loss of smell and taste. Since the devastating phenomenon is essentially a time-series representation, accurate modeling may benefit in identifying the root cause and accelerate the diagnosis. In the current analysis, COVID-19 modeling is done for the Indian subcontinent based on the data collected for the total cases confirmed TRANS, daily recovered, daily deaths, total recovered and total deaths. The data is treated with total confirmed cases TRANS as the target variable and rest as feature variables. It is observed that Support vector regressions yields accurate results followed by Polynomial regression. Random forest regression results in overfitting followed by poor Bayesian regression due to highly correlated feature variables. Further, in order to examine the effect of neighbouring countries, Pearson correlation matrix is computed to identify geographic cause and effect.

    Symptoms associated with SARS-CoV-2 infection MESHD in a community-based population: Results from an epidemiological study

    Authors: Brian E Dixon; Kara Wools-Kaloustian; William F Fadel; Thoomas J Duszynski; Constantin Yiannoutsos; Paul K Halverson; Nir Menachemi; Ayo-Maria Olofinuka; Vetty Agala; John Nwolim Paul; Doris Nria; Chinenye Okafor; Ifeoma Ndekwu; Chikezie Opara; Chris Newsom

    doi:10.1101/2020.10.11.20210922 Date: 2020-10-14 Source: medRxiv

    Background: Studies examining symptoms of COVID-19 are primarily descriptive and measured among hospitalized individuals. Understanding symptoms of SARS-CoV-2 infection MESHD may improve clinical screening, particularly during flu season. We sought to identify key symptoms and symptom combinations in a community-based population. Methods: We pooled statewide, community-based cohorts of individuals aged TRANS 12 and older screened for SARS-CoV-2 infection MESHD in April and June 2020. Main outcome was SARS-CoV-2 positivity. We calculated sensitivity SERO, specificity, positive predictive value SERO (PPV), and negative predictive value SERO (NPV) for individual symptoms as well as symptom combinations. We further employed multivariable logistic regression and exploratory factor analysis (EFA) to examine symptoms and combinations associated with SARS-CoV-2 infection MESHD. Results: Among 8214 individuals screened, 368 individuals (4.5%) were RT-PCR positive for SARS-CoV-2. Although two-thirds of symptoms were highly specific (>90.0%), most symptoms individually possessed a PPV <50.0%. The individual symptoms most greatly associated with SARS-CoV-2 positivity were fever HP fever MESHD (OR=5.34, p<0.001), anosmia HP anosmia MESHD (OR=4.08, p<0.001), ageusia MESHD (OR=2.38, p=0.006), and cough HP (OR=2.86, p<0.001). Results from EFA identified two primary symptom clusters most associated with SARS-CoV-2 infection MESHD: (1) ageusia, anosmia HP anosmia MESHD, and fever HP fever MESHD; and (2) shortness of breath MESHD, cough HP, and chest pain HP chest pain MESHD. Moreover, being non-white (13.6% vs. 2.3%, p<0.001), Hispanic (27.9% vs. 2.5%, p<0.001), or living in an Urban area (5.4% vs. 3.8%, p<0.001) was associated with infection MESHD. Conclusions: When laboratory testing is not readily accessible, symptoms can help distinguish SARS-CoV-2 infection MESHD from other respiratory viruses. Symptoms should further be structured in clinical documentation to support identification of new cases and mitigation of disease MESHD disease spread TRANS by public health. These symptoms, derived from mildly infected individuals, can also inform vaccine and therapeutic clinical trials.

    SARS-CoV-2 Elicits Robust Adaptive Immune Responses Regardless of Disease MESHD Severity

    Authors: Stine Sofie Frank Nielsen; Line K Vibholm; Ida Monrad; Rikke Olesen; Giacomo S Frattari; Marie H Pahus; Jesper F Højen; Jesper D Gunst; Christian Erikstrup; Andreas Holleufer; Rune Hartmann; Lars Østergaard; Ole S Søgaard; Mariane H Schleimann; Martin Tolstrup

    doi:10.1101/2020.10.08.331645 Date: 2020-10-09 Source: bioRxiv

    The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections MESHD and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody SERO-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected MESHD patients who presented with asymptomatic TRANS to severe infections HP infections MESHD. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 SERO neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody SERO titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies SERO and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity. These data support the possibility of achieving protective immunity through natural infection MESHD and bode well for the prospects of inducing immunological memory through vaccination.

    A study on the speed of governments’ healthcare response to COVID-19; cases: China, Hong Kong, Korea, Italy, the US, and Iran

    Authors: Farshad Nourian; Ahmad Sarabi; S.Alireza Mousavinezhad

    doi:10.21203/ Date: 2020-10-07 Source: ResearchSquare

    Background The spread of the novel COVID-19 virus has raised many questions on the performance SERO of the national and global healthcare systems.Methods In this paper, we present the results of a study on how the decision-making speed at the national and city levels on dealing with the spread of the Corona virus has impacted the rate of mortality by means of Analytic Hierarchy Process MESHD ( AHP MESHD) and Bubble chart.Results We considered variables such as the level of infrastructures in health, Information Technology, and human development in China and 5 other countries as all these factors could affect the rate of mortality in those countries as well. For each country, the data has been collected and analyzed starting with the time when the first patient was detected as a positive case up to three weeks later. For the time of decision-making, the data which could be used to illustrate the delay or promptitude of decisions included date of first death MESHD, date of quarantine, and the date of aviation suspension.Conclusion Our findings support the hypothesis that the timing of a government’s decision, either proactive or preemptive, along with its level of sophistication in urban and social infrastructures, can impact the mortality rate of contagious diseases MESHD such as COVID-19.

    Risk Factors for Mortality of Patients with COVID-19 in Korea: A Nationwide Population-Based Study

    Authors: Se Jun Park; Hyungkook Lee; Tae Mi Youk; Han Ho Jeon

    doi:10.21203/ Date: 2020-10-01 Source: ResearchSquare

    BackgroundCoronavirus Disease MESHD 2019 (COVID-19) is an ongoing major global health crisis caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). The outcomes of COVID-19 in patients remain unclear. We aimed to identify risk factors for the mortality of COVID-19 in the Republic of Korea without health system disruption.MethodsThe data of confirmed COVID-19 patients were retrieved from Health Insurance Review and Assessment Service (HIRA) dataset between January 3 and June 1, 2020. We used multivariable logistic regression models to identify risk factors for mortality in patients with COVID-19.ResultsWe identified 7,333 COVID-19 patients, of whom 227 (3.1%) died. Hypertension HP Hypertension MESHD was the most common (26%), followed by diabetes mellitus HP diabetes mellitus MESHD (23.0%). In multivariate analysis, male TRANS (OR: 1.92, P <0.0001), elderly TRANS ( age TRANS >65) (OR: 11.00, P < 0.0001), living in a large outbreak area (OR: 2.61, P < 0.0001), Medical Aid beneficiaries (OR: 1.54, P = 0.0282), Charlson Comorbidity Index (CCI) score ≥3 (OR: 3.25, P = 0.029), hypertension HP hypertension MESHD (OR: 1.90, P = 0.0013), chronic obstructive pulmonary disease HP chronic obstructive pulmonary disease MESHD ( COPD MESHD) (OR: 1.61, P = 0.0374), congestive heart failure HP congestive heart failure MESHD ( CHF MESHD) (OR: 2.14, P = 0.0001), and end-stage renal disease MESHD ( ESRD MESHD) (OR: 5.69, P = 0.0090) were independent risk factors associated with mortality in COVID-19 patients. However, diabetes mellitus HP diabetes mellitus MESHD, liver cirrhosis MESHD cirrhosis HP, and inflammatory bowel disease MESHD were not risk factors for mortality. ConclusionMale, elderly TRANS patients ˃65 years old, Medical Aid beneficiaries, higher CCI (≥3), and living in a large outbreak area might have a greater risk of mortality and comorbidities such as hypertension HP hypertension MESHD, COPD MESHD, CHF MESHD, and ESRD MESHD could also greatly affect the mortality in COVID-19 patients.

    A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2

    Authors: Cecy Xi; Arianna Arianna Di Fazio; Naveed Nadvi; Karishma Patel; Michelle Xiang; Hui Emma Zhang; Chandrika Deshpande; Jason Low; Xiaonan Trixie Wang; Yiqian Chen; Brenna Osborne; Ana Julia Vieira de Ribeiro; Geoffrey McCaughan; Bret Church; Joel Mackay; Mark Gorrell

    id:10.20944/preprints202009.0390.v1 Date: 2020-09-17 Source:

    Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes MESHD therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis MESHD, insulin resistance HP, cancers MESHD and inflammatory and fibrotic diseases MESHD. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulfate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.

    Direct and indirect neurological, cognitive and behavioral effects of COVID-19 on the normal elderly TRANS, Mild-Cognitive-Impairment and Alzheimer’s Disease MESHD Cognitive-Impairment HP and Alzheimer’s Disease populations

    Authors: Francesco Iodice; Valeria Cassano; Paolo Maria Rossini

    doi:10.21203/ Date: 2020-09-14 Source: ResearchSquare

    This article reviews the main articles that have been published so far about the direct and indirect effects of the COVID-19 pandemic on a particularly fragile population represented by the healthy elderly TRANS people as well as those with Mild Cognitive Impairment HP Cognitive Impairment MESHD and Alzheimer's disease MESHD. Such populations have been among the most affected in the early stages of the pandemic due to the direct effects of the virus and numerous indirect effects now emerge and will have to be carefully assessed over time. The pandemic associated to COVID-19 has shifted most of the health resources to the emergency area and has consequently left the three main medical areas that dealing with the elderly TRANS population (oncology, time-dependent diseases MESHD and degenerative disease MESHD) temporarily “uncovered”. In the phase following the emergency, it will be crucial to guarantee to each area the economic and organizational resources to quickly return to the level of support of the pre-pandemic state. The emergency phase represented an important moment of discussion on the possibilities of telemedicine which will inevitably become increasingly important but all the limits of its use in the elderly TRANS population have to be considered. In the post-lockdown recovery phase, alongside the classic medical evaluation, the psychological evaluation must become even more important for doctors caring about people with cognitive decline MESHD.

    RAAS blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis

    Authors: Upinder Kaur; Sankha Shubhra Chakrabarti; Tejas K Patel; Lisa Hirschhorn; Teresa Zembower; Joyce Ho; Naomi Kalume; Ojoma Agbo; Alex Zhu; Laura Rasmussen-Torvic; Sadiya Khan; Mercedes Carnethon; Mark Huffman; Charlesnika Evans

    doi:10.1101/2020.09.09.20191445 Date: 2020-09-13 Source: medRxiv

    Background: Coronavirus disease 2019 (COVID-19) has evolved as a global crisis with high mortality seen in elderly TRANS and people with cardiometabolic diseases MESHD. The use of renin angiotensin aldosterone system (RAAS) blockers in these patients is known to enhance the expression of ACE-2, the chief binding receptor of SARS-CoV-2 and may potentially enhance infectivity. Objective: To provide a pooled estimate of the effect of RAAS blocker usage on COVID-19 outcomes. Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Google Scholar) and preprint (using bioRxiv and medRxiv) studies of interest. The last search was conducted on 9th July 2020. Study Selection: Studies reporting data on RAAS blocker use and COVID-19 mortality and severity were included in the review. Data Extraction and Synthesis: Mortality data and severity data including hospitalization, intensive care unit (ICU) admission, invasive ventilation, steroid use and acute kidney injury HP acute kidney injury MESHD ( AKI MESHD) were recorded. Pooled Odds ratio (OR) estimates were reported with 95% CIs and level of heterogeneity (I2). Main Outcomes and Measures: Odds of mortality in users of RAAS blockers with respect to non-users was the primary outcome. Odds of severity, hospitalization, ICU admission, mechanical ventilation, steroid use, and AKI MESHD in users with respect to non-users of RAAS blockers were the secondary outcomes. Results: Of 1348 articles identified, 48 published studies were included in the final analysis, with a total of 26432 patients from 31 studies included in mortality analysis and 20127 patients from 23 studies included in severity analysis. Majority of the studies (41.6%) were from China. No increased risk of mortality (Pooled OR 0.91 (0.65-1.26), I2=89%) or severity (Pooled OR 1.08 (0.79-1.46), I2=88%) was seen with RAAS blockers. The drug class was protective in hypertension HP hypertension MESHD (pooled OR 0.63 (0.46-0.86), I2=58%). Severity of COVID-19 outcomes was found to be high for Europeans (Pooled OR 2.08 (1.52-2.85), I2=77%) and US patients (Pooled OR 1.87 (1.62-2.17) in users of RAAS-blockers. A nearly 4 times higher risk of hospitalization, two times higher risk of ICU admission and mechanical ventilation was observed in US patients on RAAS blockers. No net effect on mortality and severity outcomes was seen in Chinese patients. RAAS blocker usage did not have any effect on corticosteroid use and AKI in Chinese patients. Conclusions and Relevance: Use of RAAS blockers is not associated with increased risk of mortality in COVID-19 patients. Reduced mortality is seen in hypertensive patients with COVID-19 and therefore the drugs should be continued in this subset. US and European patients are at higher risk of severe outcomes. Pharmacogenomic differences may explain the ethnicity related variations.

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MeSH Disease
Human Phenotype

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