Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 21
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    Clinical Characteristics and outcomes in HBV carriers TRANS with COVID-19 in WuHan, China: a retrospective cohort study

    Authors: Jingjing Lu; Mu Hu; Xia Zhou; Hui Zhu; Feilong Wang; Jianhao Huang; Zhongliang Guo; Qiang Li; Qi Yin; Zhifeng Yang

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    Background: Coronavirus 2019 (COVID-19) is a novel infectious disease MESHD that was first reported in Wuhan, China, but has spread to all parts of the world. At the same time, because China has millions of HBV carriers TRANS, HBV infection MESHD has become a major public health problem in China. In this study, we aim to describe the clinical features of HBV carriers TRANS (AsC) infected with COVID-19 and to assess the factors that may affect the outcome during disease progression MESHD.Methods: This retrospective cohort study included 72 patients diagnosed with COVID-19 in Wuhan Jinyintan Hospital. These patients were also diagnosed as HBV carriers TRANS. The epidemiological characteristics, demographic features, clinical manifestations, laboratory test, treatment, management and final outcome were collected and analyzed.Results: The median age TRANS of 72 patients is 58.5 years old, of which 55.56% (n=40) are male TRANS. 20 (30.56%) patients were severe cases and 50 (69.44%) were non-severe cases. Fever MESHD Fever HP is the most common symptom, followed by cough MESHD cough HP, chest tightness HP and sputum. Laboratory test results including hematologic, biochemical, infection MESHD and coagulation parameters and several indicators, such as Aspartate Aminotransferase (AST), Total Bilirubin (TBil), Direct Bilirubin (DBil), Indirect Bilirubin (IBil), γ-glutamyl Transferase (GGT) showed difference between their admission and discharge. The level of Prealbumin (PA) and Serum SERO Amyloid A (SAA) in the study showed a significant trend from high to low, which has statistical significance.Conclusions: The clinical features of HBV carriers TRANS with COVID-19 have obvious systemic symptoms, such as fever MESHD fever HP, cough MESHD cough HP, and chest tightness HP. Compared with liver function data on admission and discharge, SARS-CoV-2 does not directly activate the Hepatitis B MESHD Hepatitis HP virus, and the risk of liver cell damage of HBV carriers TRANS with COVID-19 does not increase. Both PA and SAA are sensitive indicators and can be used to evaluate the prognosis and outcome of these patients.

    Prioritization of Potential Drugs Targeting the SARS-CoV-2 Main Protease

    Authors: Yanjin Li; Yu Zhang; Yikai Han; Tengfei Zhang; Ranran Du

    doi:10.26434/chemrxiv.12629858.v1 Date: 2020-07-09 Source: ChemRxiv

    Since its outbreak in 2019, the acute respiratory syndrome MESHD caused by SARS-Cov-2 has become a severe global threat to human. The lack of effective drugs strongly limits the therapeutic treatment against this pandemic disease MESHD. Here we employed a computational approach to prioritize potential inhibitors that directly target the core enzyme of SARS-Cov-2, the main protease, which is responsible for processing the viral RNA-translated polyprotein into functional proteins for viral replication. Based on a large-scale screening of over 13, 000 drug-like molecules, we have identified the most potential drugs that may suffice drug repurposing for SARS-Cov-2. Importantly, the second top hit is Beclabuvir, a known replication inhibitor of hepatitis C MESHD hepatitis HP virus (HCV), which is recently reported to inhibit SARS-Cov-2 as well. We also noted several neurotransmitter-related ligands among the top candidates, suggesting a novel molecular similarity between this respiratory syndrome MESHD and neural activities. Our approach not only provides a comprehensive list of prioritized drug candidates for SARS-Cov-2, but also reveals intriguing molecular patterns that are worth future explorations.

    Poor Outcomes in Patients with Cirrhosis HP and COVID-19

    Authors: Shalimar; Anshuman Elhence; Manas Vaishnav; Ramesh Kumar; Piyush Pathak; Kapil Dev Soni; Richa Aggarwal; Manish Soneja; Pankaj Jorwal; Arvind Kumar; Puneet Khanna; Akhil Kant Singh; Ashutosh Biswas; Neeraj Nischal; Lalit Dhar; Aashish Choudhary; Krithika Rangarajan; Anant Mohan; Pragyan Acharya; Baibaswata Nayak; Deepak Gunjan; Anoop Saraya; Soumya Mahapatra; Govind Makharia; Anjan Trikha; Pramod Garg

    doi:10.21203/ Date: 2020-07-06 Source: ResearchSquare

    Background and AimThere is a paucity of data on the clinical presentations and outcomes of Coronavirus disease MESHD 2019(COVID-19) in patients with underlying liver disease MESHD. We aimed to summarize the presentations and outcomes of COVID-19 positive patients and compare with historical controls.MethodsPatients with known chronic liver disease MESHD who presented with superimposed COVID- 19(n=28) between 22nd April and 22nd June 2020 were studied. Seventy-eight cirrhotic patients from historical controls were taken as comparison group.ResultsA total of 28 COVID patients- two without cirrhosis HP, one with compensated cirrhosis HP, sixteen with acute decompensation (AD), and nine with acute-on-chronic liver failure MESHD(ACLF) were included. The etiology of cirrhosis HP was alcohol(n=9), non-alcoholic fatty liver disease MESHD(n=2), viral(n=5), autoimmune hepatitis MESHD hepatitis HP(n=4), and cryptogenic cirrhosis HP(n=6). The clinical presentations included complications of cirrhosis HP in 12(46.2%), respiratory symptoms in 3(11.5%) and combined complications of cirrhosis HP and respiratory symptoms in 11(42.3%) patients. The median hospital stay was 8(7-12) days. The mortality rate in COVID-19 patients was 42.3%(11/26), as compared to 23.1%(18/78) in the historical controls(p=0.077). All COVID-19 patients with ACLF(9/9) died compared to 53.3%(16/30) in ACLF of historical controls(p=0.015). Mortality rate was higher in COVID patients with compensated cirrhosis HP and AD as compared to historical controls 2/17(11.8%) vs 2/48(4.2%), though not statistically significant (p=0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio, 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully.ConclusionCOVID-19 is associated with poor outcomes in patients with cirrhosis HP, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

    A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19

    Authors: Fernando Santos-Beneit; Vytautas Raškevičius; Vytenis A. Skeberdis; Sergio Bordel

    doi:10.21203/ Date: 2020-06-18 Source: ResearchSquare

    In this study we have developed a metabolic modeling approach to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue MESHD, Zika, Hepatitis C MESHD Hepatitis HP and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as propylthiouracil, 2-bromopalmitate, lipofermata, tunicamycin, benzyl isothiocyanate, tipifarnib and lonafarnib) are also proposed.

    Non-coronavirus Genome Sequences Identified from Metagenomic Analysis of Clinical Samples from COVID-19 Infected Patients: An Evidence for Co- infection MESHD

    Authors: Mohamed Abouelkhair

    id:10.20944/preprints202005.0505.v2 Date: 2020-06-18 Source:

    In December 2019, pneumonia MESHD pneumonia HP caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus MESHD disease MESHD 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency MESHD. Cellular co- infection MESHD is a critical determinant of both viral fitness and infection MESHD outcome and plays a crucial role in shaping the host immune response to infections MESHD. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency HP virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis MESHD hepatitis MESHD hepatitis HP virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

    Novel Method for Detection of Genes With Altered Expression Caused by Coronavirus Infection MESHD and Screening of Candidate Drugs for SARS-CoV-2

    Authors: Y-H. Taguchi; Turki Turki

    id:10.20944/preprints202004.0431.v2 Date: 2020-06-17 Source:

    To better understand the genes with altered expression caused by infection MESHD with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease MESHD, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection MESHD of mouse hepatitis MESHD hepatitis MESHD hepatitis HP virus, which is regarded as a suitable model of human coronavirus infection MESHD. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection MESHD, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an \textit{in silico} method to identify candidate drugs for treating COVID-19.

    Predicting inhibitors for SARS-CoV-2 RNA-dependent RNA polymerase using machine learning and virtual screening

    Authors: Romeo Cozac; Nazim Medzhidov; Shinya Yuki

    id:2006.06523v1 Date: 2020-06-09 Source: arXiv

    Global coronavirus disease MESHD pandemic (COVID-19) caused by newly identified SARS- CoV-2 coronavirus continues to claim the lives of thousands of people worldwide. The unavailability of specific medications to treat COVID-19 has led to drug repositioning efforts using various approaches, including computational analyses. Such analyses mostly rely on molecular docking and require the 3D structure of the target protein to be available. In this study, we utilized a set of machine learning algorithms and trained them on a dataset of RNA-dependent RNA polymerase (RdRp) inhibitors to run inference analyses on antiviral and anti-inflammatory drugs solely based on the ligand information. We also performed virtual screening analysis of the drug candidates predicted by machine learning models and docked them against the active site of SARS- CoV-2 RdRp, a key component of the virus replication machinery. Based on the ligand information of RdRp inhibitors, the machine learning models were able to identify candidates such as remdesivir and baloxavir marboxil, molecules with documented activity against RdRp of the novel coronavirus. Among the other identified drug candidates were beclabuvir, a non-nucleoside inhibitor of the hepatitis C MESHD hepatitis HP virus (HCV) RdRp enzyme, and HCV protease inhibitors paritaprevir and faldaprevir. Further analysis of these candidates using molecular docking against the SARS-CoV-2 RdRp revealed low binding energies against the enzyme active site. Our approach also identified anti-inflammatory drugs lupeol, lifitegrast, antrafenine, betulinic acid, and ursolic acid to have potential activity against SARS-CoV-2 RdRp. We propose that the results of this study are considered for further validation as potential therapeutic options against COVID-19.

    Protective roles of flu infections MESHD and BCG vaccination in lowering Covid-19 mortality

    Authors: Sanmoy Pathak; Mohit Kumar Jolly; Dipankar Nandi

    doi:10.21203/ Date: 2020-06-04 Source: ResearchSquare

    The recent Covid-19 pandemic has caused a great loss of lives as well as affected economies in several countries. The loss of Covid-19 deaths MESHD is far greater in some countries compared to others. This observation led us to perform epidemiological analysis using disease MESHD and vaccination data in the public domain with respect to measles MESHD, hepatitis B MESHD hepatitis HP virus, polio, tuberculosis MESHD and flu from twenty five countries across the globe. There is no correlation between Covid-19 incidences or deaths MESHD, as well as vaccination coverage, with respect to diseases MESHD such as measles MESHD, hepatitis B MESHD hepatitis HP virus and polio. However, countries with lower cases of tuberculosis MESHD and higher cases of flu have a significant correlation with respect to Covid-19 deaths MESHD. In fact, countries with high BCG vaccination coverage show a significant negative correlation with Covid-19 deaths MESHD. Surprisingly, countries such as the USA, Italy, France and Spain which have flu vaccination, but not BCG vaccination, show maximum number of Covid-19 deaths MESHD. It appears that high numbers of flu infections MESHD are protective and can decrease the number of Covid-19 deaths MESHD. Importantly, countries with high flu cases and BCG vaccination, such as India, Egypt, South Africa etc, show relatively lower Covid-19 deaths MESHD, reinforcing the protective roles of BCG vaccination. Notably, these general trends are statistically significant for Covid-19 deaths MESHD but not Covid-19 incidences. The implications of our results are discussed with respect to the roles of microbial infections in the respiratory tract MESHD infections in the respiratory tract HP, vaccinations and other factors in lowering Covid-19 deaths MESHD.

    Combined Use of Amentoflavone and Ledipasvir Could Interfere with Binding of Spike Glycoprotein of SARS-CoV-2 to ACE2: The Results of Molecular Docking Study

    Authors: Kateryna Miroshnychenko; Anna V. Shestopalova

    doi:10.26434/chemrxiv.12377870.v1 Date: 2020-05-29 Source: ChemRxiv

    In this study we used molecular docking method to test 248 drugs related to the virus research against spike glycoprotein of SARS-CoV-2. For ten top-ranked drugs the binding sites and interactions with spike glycoprotein were analyzed in detail. The best-scored ligand is the natural biflavonoid amentoflavone. Nine of twelve top-ranked ligands are drugs used for hepatitis C MESHD hepatitis HP treatment. Among them are ledipasvir, paritaprevir, elbasvir, simeprevir, velpatasvir, glecaprevir and pibrentasvir. The two first-ranked ligands (amentoflavone and ledipasvir) have different binding sites, so their combined use may be effective, but the careful testing is required. We encourage other researchers to explore the combination of amentoflavone and ledipasvir against SARS-CoV-2 in vitro and in vivo.

    In silico screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus

    Authors: Pukar Khanal; Taaza Duyu; BM Patil; Yadu Nandan Dey; Ismail Pasha; Rohini S. Kavalapure

    doi:10.21203/ Date: 2020-05-28 Source: ResearchSquare

    Aim. The present study was aimed to identify the lead hits from reported anti-viral Indian medicinal plants to modulate the proteins through the JAK-STAT pathway and to identify the proteins that share the domain with coronavirus (COVID19) associated proteins i.e. 3CLpro, PLpro, and spike protein. Methods. The reported anti-viral plants were screened from the available databases and published literature; their phytoconstituents were retrieved, gene-expression was predicted and the modulated proteins in JAK-STAT pathway were predicted. The interaction between proteins was evaluated using STRING and the network between phytoconstituents and proteins was constructed using Cytoscape. The druglikeness score was predicted using MolSoft and the ADMET profile of phytoconstituents was evaluated using admetSAR2.0. The domain of three proteins i.e. 3CLpro, PLpro, and spike protein of coronavirus was compared using NCBI blastP against the RCSB database. Results. The majority of the phytoconstituents from the anti-viral plants were predicted to target TRAF5 protein in the JAK-STAT pathway; among them, vitexilactone was predicted to possess the highest druglikeness score. Proteins targeted in the JAK-STAT pathways were also predicted to modulate the immune system. Similarly, the docking study identified sesaminol 2-O-β-D-gentiobioside to possess the highest binding affinity with spike protein. Similarly, phylogeny comparison also identified the common protein domains with other stains of microbes like murine hepatitis MESHD hepatitis MESHD hepatitis HP virus strain A59, avian infectious bronchitis MESHD bronchitis HP virus, and porcine epidemic diarrhea MESHD diarrhea HP virus CV777. Conclusion. Although, the present study is based on computer simulations and database mining, it provides two important aspects in identifying the lead hits against coronavirus. First, targeting the JAK-STAT pathway in the corona-infected host by folk anti-viral agents can regulate the immune system which would inhibit spreading the virus inside the subject. Secondly, the well-known targets of coronavirus i.e. 3CLpro, PLpro, and spike protein share some common domains with other proteins of different microbial strains.

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MeSH Disease
Human Phenotype

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