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    Autoantibody-negative insulin-dependent Diabetes after COVID-19

    Authors: Tim Hollstein; Juliane Schulz; Andreas Glück; Dominik M Schulte; Stefan Schreiber; Stefan R Bornstein; Matthias Laudes

    doi:10.21203/rs.3.rs-39343/v1 Date: 2020-07-01 Source: ResearchSquare

    Here we report the manifestation of insulin dependent diabetes after a COVID-19 infection MESHD in the absence of typical autoantibodies for type 1 diabetes. A 19-year-old Caucasian male TRANS subject presented to our emergency MESHD department with diabetic ketoacidosis MESHD diabetic ketoacidosis HP (DKA). C-peptide levels accounted to 0.62µg/L in the presence of blood SERO glucose concentrations of 30.6 mmol/L (552 mg/dL). The patient´s case history revealed a COVID-19 disease MESHD 6-8 weeks prior to admission. This is of interest, since COVID-19 internalization into host cells is mediated via Angiotensin-converting enzyme 2 (ACE2) [1], a transmembrane glycoprotein which amongst others is crucial for β-cell homeostasis and function [2,3,4]. Detailed laboratory testing was performed, revealing no serum SERO- antibodies SERO against islet-cells (ICA), glutamic acid decarboxylase (GAD65-AA), tyrosine phosphatase (IA-2-AA), insulin (IAA) and zinc-transport-8 (ZnT8-AA), but against COVID-19. Hence, this is a presentation of an insulin-dependent diabetes mellitus MESHD diabetes mellitus HP in the absence of markers of autoimmunity HP, which might suggest direct cytolytic effects of COVID-19 on pancreatic β-cells presumably mediated via ACE2.

    Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

    Authors: Mohammad Mostafa Pourseif; Sepideh Parvizpour; Behzad Jafari; Jaber Dehghani; Behrooz Naghili; Yadollah Omidi

    doi:10.21203/rs.3.rs-32539/v1 Date: 2020-05-30 Source: ResearchSquare

    Coronavirus disease MESHD 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 253,381 deaths MESHD worldwide since its emergence in late 2019 (updated May 6th, 2020). COVID-19 is caused by a novel emerged coronavirus named as Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. In this study, we have targeted spike (S) glycoprotein, as an important surface antigen of SARS-CoV-2, to identify its immunodominant B- and T-cell epitopes. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity HP, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in the animal studies. 

    Epitope‐based peptide vaccine design against spike protein (S) of novel coronavirus (2019-nCoV): an immunoinformatics approach

    Authors: Eman Ali Awadelkareem; Nisreen Osman Mohammed; Bothina Bakor Mohammed Gaafar; Zahra - Abdelmagid; Sumaia AwadElkariem Ali

    doi:10.21203/rs.3.rs-30076/v1 Date: 2020-05-19 Source: ResearchSquare

    Background Recently the global pandemic caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has generated a significant need on identifying drugs or vaccines to prevent or reduce clinical infection MESHD of Coronavirus disease MESHD – 2019 (COVID-19). In this study, immuno-informatics tools were utilized to design a potential multi-epitopes vaccine against SARS-CoV-2 spike S protein. Structural analysis for SARS-CoV-2 spike S protein was also conducted.Method: SARS-CoV-2 spike S protein sequences were retrieved from the GeneBank of National Central Biotechnology Information (NCBI). Immune Epitope Database (IEDB) tools were used to predict B and T cell epitopes, to evaluate their allergenicity, toxicity and cross- reactivity and to calculate population coverage. Protparm sever was applied to determine protein characterization of spike protein and predicted epitopes. Molecular docking for the proposed MHCI epitopes were also achieved against Tall like Receptor (TLR8) receptors and HLA-B7 allele.Result Immuno-informatics analysis of S protein using IEDB identified only one B cell epitope 1054QSAPH1058 as linear, surface and antigenic. Although 1054QSAPH1058 was estimated as non-allergic and non-toxic, it showed protein instability. Moreover, around 45 discontinuous epitopes were also recognized as different exposed surface area. In MHCI methods, six conserved stable and safe epitopes (898FAMQMAYRF906, 258WTAGAAAYY266 and 2FVFLVLLPL10, 202 KIYSKHTPI210, 712IAIPTNFTI720 and 1060VVFLHVTYV1068) were identified. These epitopes showed strong interaction when docked with TLR8 and HLA-B7 allele especially 1060VVFLHVTYV1068 and 2FVFLVLLPL10 epitopes. Three epitopes were also predicted (898FAMQMAYRF906, 888FGAGAALQI896 and 342FNATRFASV350) using MHCII methods. Furthermore, the potential multi-epitopes were acquired by assessing allergenicity, toxicity and cross-reactivity to prevent autoimmunity HP.Conclusion The multi-epitopes vaccine was predicted based on Bioinformatics tools that may provide reliable results in a shorter time and at a lower cost. However, further in vivo and in vitro studies are required to validate their effectiveness.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).

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MeSH Disease
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