Corpus overview


MeSH Disease

Human Phenotype


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    Prediction of Single Point Mutations in Ganglioside-Binding Domain of SARS-CoV-2 S and Their Effects on Binding of 9-O-Acetylated Sialic Acid and Hidroxychloroquine

    Authors: Petar M. Mitrasinovic

    doi:10.26434/chemrxiv.12765953.v1 Date: 2020-08-06 Source: ChemRxiv

    The infectious disease MESHD CoViD-19 is caused by a new severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), also referred to as hCoV-19. A possible infection MESHD mechanism includes dual host receptor recognitions by the SARS-CoV-2 transmembrane spike (S) glycoproteins. SARS-CoV-2 S contains two different domains, the receptor-binding domain (RBD) and the N-terminal domain (NTD), which interact with the angiotensin-converting enzyme 2 (ACE2) and the ganglioside-rich domain of the plasma SERO membrane at the surface of respiratory cell, respectively. The NTD amino acid residues (111-162) form a functional ganglioside-binding domain (GBD) that is conserved in all clinical isolates. Herein, the single point mutations (SPMs) of the GBD residues to which the virus is prone during genetic adaptation are predicted using an in silico protein engineering approach. Consequently, their effects on the attachment of SARS-CoV-2 S to the ganglioside-linked 9-O-acetylated sialic acid (9-O-Ac-Sia) are explored using molecular docking simulations. Val120Tyr and Asn122Trp are found to be the most likely SPMs in the GBD of SARS-CoV-2 S being involved in very specific recognition with 9-O-Ac-Sia through electrostatic interactions. Val120Tyr and Asn122Trp are also found to be the most likely SPMs in the GBD of SARS-CoV-2 S that is involved in conspicuously hydrophobic recognition with hidroxychloroquine (Hcq), thereby indicating the ability of Hcq to competitively inhibit GBD interactions with lipid rafts. However, the considerably non-specific binding of Hcq and the micromolar range of the dissociation constants of the SARS-CoV-2 S/Hcq complexes do not support the proposal of treating Hcq as a drug candidate. Maintaining a clear resemblance of the structure of a potential drug candidate to a natural substrate, accompanied by essential functional group modifications, may be a usable guideline for the structure-based design of anti-CoViD-19 drugs.

    Correlation based analysis of COVID-19 virus genome versus other fatal virus genomes

    Authors: Sidharth Purohit; Suresh Chandra Satapathy; Sibi Chakkaravarthy S; Yu-Dong Zhang

    doi:10.21203/ Date: 2020-08-06 Source: ResearchSquare

    Virus attacks have had devastating effects on mankind. The prominent viruses such as Ebola virus (2012), SARS-CoV or Severe acute respiratory syndrome MESHD, Middle East respiratory syndrome MESHD-related coronavirus called as the MERS (EMC/2012), Spanish flu (H1N1 virus-1918) and the most recent COVID-19(SARS-CoV-2) are the ones that have created a difficult situation for the survival of the human race.Background: Currently, throughout the world, a global pandemic situation has put economy, livelihood, and human existence in a very pathetic situation. Most of the above-mentioned viruses exhibit some similar characteristics and genetic pattern. Analyzing such characteristics and genetic pattern can help the researchers to get a deeper insight into the viruses and helps in finding appropriate medicine or cure.Methods: To address these issues, this paper proposes an experimental analysis of the above-mentioned viruses data using correlation methods. The virus data considered for the experimental analysis includes the distribution of various amino acids, protein sequences, 3D modelling of viruses, pairwise alignment of proteins that comprise the DNA genome of the viruses. Furthermore, this comparative analysis can be used by the researchers and organizations like WHO(World Health Organization), computational biologists, genetic engineers to frame a layout for studying the DNA sequence distribution, percentage of GC (Guanine-Cytosine) protein which determines the heat stability of viruses. We have used the BioPython to illustrate the gene study of prominent viruses and have derived results and insights in the form of 3D modelling.Results: The experimental results are more promising with an accuracy rate of 96% in overall virus relationship calculation.

    Comparative Evaluation of Three Serologic Assays for the Identification of SARS-CoV-2 Antibodies SERO

    Authors: Keenan O. Hogan; Dave Klippel; Fred V. Plapp; Rachael M. Liesman

    doi:10.1101/2020.08.04.20167643 Date: 2020-08-05 Source: medRxiv

    Background and aims Serologic assays for the detection of severe acute respiratory syndrome MESHD coronavirus 2 ( SARS-CoV-2) antibodies SERO are being developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component to pandemic management and public health. Materials and methods Residual serum samples SERO (N=113) from patients who were evaluated for SARS-CoV-2 infection MESHD status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody SERO, and Access SARS-CoV-2 IgG. Results Testing of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR). Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay. Conclusion This study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.

    Alveolitis in severe SARS-CoV-2 pneumonia MESHD pneumonia HP is driven by self-sustaining circuits between infected alveolar macrophages and T cells

    Authors: Rogan A Grant; Luisa Morales-Nebreda; Nikolay S Markov; Suchitra Swaminathan; Estefany R Guzman; Darryl A Abbott; Helen K Donnelly; Alvaro Donayre; Isaac A Goldberg; Zasu M Klug; Nicole Borkowski; Ziyan Lu; Hermon Kihshen; Yuliya Politanska; Lango Sichizya; Mengjia Kang; Ali Shilatifard; Chao Qi; A Christine Argento; Jacqueline M Kruser; Elizabeth S Malsin; Chiagozie O Pickens; Sean Smith; James M Walter; Anna E Pawlowski; Daniel Schneider; Prasanth Nannapaneni; Hiam Abdala-Valencia; Ankit Bharat; Cara J Gottardi; GR Scott Budinger; Alexander A Misharin; Benjamin David Singer; Richard G Wunderink; - The NU SCRIPT Study Investigators

    doi:10.1101/2020.08.05.238188 Date: 2020-08-05 Source: bioRxiv

    Some patients infected with Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARS-CoV-2) develop severe pneumonia MESHD pneumonia HP and the acute respiratory distress HP syndrome MESHD (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia MESHD pneumonia HP. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure HP and 252 patients with known or suspected pneumonia MESHD pneumonia HP from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection MESHD at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia HP. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation MESHD.

    Analysis of the potential impact of genomic variants in SARS-CoV-2 genomes from India on molecular diagnostic assays

    Authors: Abhinav Jain; Mercy Rophina; Saurabh Mahajan; Bhavya Balaji Krishnan; Manasa Sharma; Sreya Mandal; Teresa Fernandez; Sumayra Sultanji; Samatha Mathew; Sridhar Sivasubbu; Vinod Scaria

    doi:10.1101/2020.08.05.238618 Date: 2020-08-05 Source: bioRxiv

    An isolated epidemic of Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) causing Coronavirus Diseases MESHD (C0VID-19) originating in Wuhan, China has now rapidly emerged into a global pandemic affecting millions of people worldwide. Molecular detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) forms the mainstay in screening, diagnosis and epidemiology of disease MESHD. The virus has been evolving through base substitutions. The recent availability of genomes of SARS-CoV-2 isolates from different countries including India motivated us to assess the presence and potential impact of variations in target sites for the oligonucleotide primers and probes used in molecular diagnosis. We catalogued a total of 132 primers or probes sequences from the literature and the public domain. Our analysis revealed a total of 125 unique genetic variants in 80 either primers or probes binding sites. A total of 13 unique variants had allele frequency of [≥] 1% in Indian SARS-CoV-2 genomes mapped to the primers or probes binding sites. A total of 15 primers or probes binding sites had cumulative variant frequency of [≥] 1% in the SARS-CoV-2 genomes. These included primers or probes sites which are widely used in India and across the world for molecular diagnosis as well as approved by national and international agencies. This highlights the need for sequencing genomes of emerging pathogens to make evidence based policies for development and approval of diagnostics. To the best of our knowledge, ours is the most comprehensive analysis of genomic variants in genomes of SARS-CoV-2 isolates from India and their potential impact on efficacy of molecular diagnostics. Keywords: COVID-19, genomes, SARS-CoV-2, variations, reverse transcription polymerase chain reaction, Gibbs free energy

    Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

    Authors: Markus Hoffmann; Heike Hofmann-Winkler; Joan C. Smith; Nadine Krueger; Lambert K. Sorensen; Ole S. Sogaard; Jorgen Bo Hasselstrom; Michael Winkler; Tim Hempel; Lluis Raich; Simon Olsson; Takashi Yamazoe; Katsura Yamatsuta; Hirotaka Mizuno; Stephan Ludwig; Frank Noe; Jason M. Sheltzer; Mads Kjolby; Stefan Poehlmann

    doi:10.1101/2020.08.05.237651 Date: 2020-08-05 Source: bioRxiv

    Antiviral therapy is urgently needed to combat the coronavirus disease MESHD 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The protease inhibitor camostat mesylate inhibits SARS-CoV-2 infection MESHD of lung cells by blocking the virus-activating host cell protease TMPRSS2. Camostat mesylate has been approved for treatment of pancreatitis MESHD pancreatitis HP in Japan and is currently being repurposed for COVID-19 treatment. However, potential mechanisms of viral resistance as well as camostat mesylate metabolization and antiviral activity of metabolites are unclear. Here, we show that SARS-CoV-2 can employ TMPRSS2-related host cell proteases for activation and that several of them are expressed in viral target cells. However, entry mediated by these proteases was blocked by camostat mesylate. The camostat metabolite GBPA inhibited the activity of recombinant TMPRSS2 with reduced efficiency as compared to camostat mesylate and was rapidly generated in the presence of serum SERO. Importantly, the infection MESHD experiments in which camostat mesylate was identified as a SARS-CoV-2 inhibitor involved preincubation of target cells with camostat mesylate in the presence of serum SERO for 2 h and thus allowed conversion of camostat mesylate into GBPA. Indeed, when the antiviral activities of GBPA and camostat mesylate were compared in this setting, no major differences were identified. Our results indicate that use of TMPRSS2-related proteases for entry into target cells will not render SARS-CoV-2 camostat mesylate resistant. Moreover, the present and previous findings suggest that the peak concentrations of GBPA established after the clinically approved camostat mesylate dose (600 mg/day) will result in antiviral activity.

    Knowledge and attitude of dentists, dental auxiliaries and students regarding the COVID-19 pandemic in Saudi Arabia: A Cross-Sectional Survey

    Authors: Suliman Shahin; Amr Bugshan; Khalid Almulhim; Mishali AlSharief; Yousif Al-Dulaijan; Faisal al-Qarni

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    Background: This study aimed to assess the knowledge and attitude of dental professionals in Saudi Arabia regarding severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and coronavirus disease MESHD 2019 (COVID-19).Methods: A questionnaire was developed to assess various dental professionals from both governmental and private sectors through online and social media outlets. Results: A total of 1,033 responses were collected. Moreover, 63.4% of respondents (63.4%) were working in hospitals. Of all respondents, 44.9%, 33.4%, and 21.7% were in governmental clinics, academia, and private sector, respectively. Overall knowledge on incubation period TRANS and route of transmission TRANS of SARS-CoV-2 was satisfactory across all dental professions. All dental professionals except for dental assistants demonstrated adequate knowledge on the recommended hand-soap cleaning time (p < 0.001). Most dental professionals displayed unsatisfactory knowledge and disagreement on the survival of SARS-CoV-2 outside the host (p < 0.001). Furthermore, 75.1% of respondents were reluctant to treat a suspected COVID-19 patient, and 92% participants believed that the mode of transmission TRANS was droplet inhalation. Fever MESHD Fever HP, coughing MESHD coughing HP, and shortness of breath were identified as the most common symptoms of COVID-19. Most standard methods of prevention in the dental office were selected by at least 50% of participants. Conclusions: An appropriate level of knowledge on SARS-CoV-2 incubation period TRANS and signs and symptoms MESHD of COVID-19 was noted among all dental professionals in Saudi Arabia. Perceived survival outside the host was modest. A certain level of apprehension toward suspected SARS-CoV-2 patients existed among most professionals. Pandemic-awareness campaigns are essential among healthcare providers.

    Spatial Distribution and Trend Analysis of Current Status of COVID-19 in Nepal and Global Future Preventive Perspectives

    Authors: Ramesh Raj Pant; Buddha Bahadur Bahadur; Kiran Bishwakarma; Sudip Paudel; Nashib Pandey; Samir Kumar Adhikari; Kamal Ranabhat

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    Background: Coronavirus disease MESHD (COVID-19) is a recently discovered severe and contagious disease MESHD caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and has received worldwide attention. The risk of COVID-19 is serious for the infected persons of chronic diseases MESHD as well as vulnerable populations including elder group. Still, the present scenario of scarcity of effective treatment options and limited recovery rate of ongoing treatment are prevailed in Nepal. This study aims to analyze the spatial distribution and trends of COVID-19 with the help of geographic information system (GIS) software and outlook future preventive perspectives.Methods: In this research work, we used GIS tool ArcGIS 10.4.1 to map the distribution patterns of population of COVID-19 cases. Federal, provincial and district level daily cases data of COVID-19 confirmed, cured and death MESHD from 23rd January to 13th July 2020 were obtained from the Ministry of Health and Population (MoHP), Government of Nepal. In addition, we reviewed several peer-reviewed research papers to summarize the global scenarios and preventive perspectives on COVID-19.Results: In context to Nepal SARS-CoV-2 has spread throughout the country infecting 16,945 persons in all 77 districts, as of 13th July, 2020. Confirmed, cured and death MESHD cases experienced an upward trend up to 1st July, 2020 followed by downward trend as of 13th July, 2020. Over 70% of total confirmed cases TRANS of reported COVID-19 patients were from the lowland-plain area. Spatial clustering suggested that provinces 2 and 5 were at potentially increased risk of COVID-19, and Province 1 and Bagmati province could be grouped as future "hot spots". In addition, we proposed four strategies namely, identification of the key medical and social elements, discovery and development of treatment options for a future pandemic, investing in ethno-medicine research and epidemic preparedness of health care system to decrease the efficacy of calamities of future pandemics.Conclusion: Our study demonstrates one of the best ways to protect; control and sluggish transmission TRANS of SARS-CoV-2 could be achieved by monitoring active ties using GIS spatial analysis. And, the severity of future pandemic could be minimized by integrative action on the abovementioned four different preventive master plans.

    Lymphopenia MESHD Lymphopenia HP-induced T cell proliferation is a hallmark of severe COVID-19

    Authors: Sarah Adamo; Stéphane Chevrier; Carlo Cervia; Yves Zurbuchen; Miro E. Räber; Liliane Yang; Sujana Sivapatham; Andrea Jacobs; Esther Bächli; Alain Rudiger; Melina Stüssi-Helbling; Lars C. Huber; Dominik Schaer; Bernd Bodenmiller; Onur Boyman; Jakob Nilsson

    doi:10.1101/2020.08.04.236521 Date: 2020-08-04 Source: bioRxiv

    Coronavirus disease MESHD 2019 (COVID-19), caused by infection MESHD infection with severe HP with severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), has a broad clinical presentation ranging from asymptomatic infection MESHD asymptomatic TRANS to fatal disease MESHD. Different features associated with the immune response to SARS-CoV-2, such as hyperinflammation and reduction of peripheral CD8+ T cell counts are strongly associated with severe disease MESHD. Here, we confirm the reduction in peripheral CD8+ T cells both in relative and absolute terms and identify T cell apoptosis and migration into inflamed tissues as possible mechanisms driving peripheral T cell lymphopenia MESHD lymphopenia HP. Furthermore, we find evidence of elevated serum SERO interleukin-7, thus indicating systemic T cell paucity and signs of increased T cell proliferation in patients with severe lymphopenia MESHD lymphopenia HP. Following T cell lymphopenia MESHD lymphopenia HP in our pseudo-longitudinal time course, we observed expansion and recovery of poly-specific antiviral T cells, thus arguing for lymphopenia MESHD lymphopenia HP-induced T cell proliferation. In summary, this study suggests that extensive T cell loss and subsequent T cell proliferation are characteristic of severe COVID-19.

    Trends of Interventional Radiology procedures during the Covid-19 pandemic: The first 27 weeks in the eye of the storm

    Authors: Guo Yuan How; Uei Pua

    doi:10.21203/ Date: 2020-08-04 Source: ResearchSquare

    ObjectivesWhile the Novel Coronavirus (COVID-19) pandemic looks to persist, institutions promote delaying procedures. Understanding trends and demands of interventional radiology (IR) procedures in the infected and COVID-free populations are needed in long-term planning. We detail IR procedure trends in the first 27 weeks of the pandemic and compare with the pre-pandemic era. MethodsIn this IRB approved retrospective electronic case review, all IR patients in our institution from 1 January to 9 July 2020, the same period in 2019 pre-pandemic and the Severe Acute Respiratory Syndrome MESHD (SARS-CoV) outbreak were included. IR procedures were classified using Interventional Radiology – Procedure Acuity Scale (IR-PAS) and category of IR procedures. Along with descriptive frequencies, the Mann-Whitney U test and Chi-square test of independence were performed.ResultsDuring the pandemic, 3655 IR procedures were performed compared to 3851 procedures pre-pandemic. No statistically significant difference in weekly IR caseloads across IR-PAS tiers between both periods (p = .088) and category of procedure (p = .054) were noted. General intervention procedures remained the largest proportion and musculoskeletal procedures the minority, in both periods. More general intervention radiology and oncology procedures were performed during the Covid-19 pandemic compared to the SARS-CoV outbreak. Thirty-four (0.93%) IR procedures were performed on 30 COVID-19 patients. There was no IR procedure-related COVID-19 cross- transmission TRANS. ConclusionsDemand for IR procedures among COVID-free patients remains high, and IR procedures involving COVID-19 represents a fraction of the IR caseload. A sustainable model in providing timely IR services to COVID-free patients needs to be considered.

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MeSH Disease
Human Phenotype

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