scholarly journals Linking COVID-19 and heme-driven pathophysiologies: A combined computational-experimental approach

2021 ◽  
Author(s):  
Marie-T. Hopp ◽  
Daniel Domingo-Fernandez ◽  
Yojana Gadiya ◽  
Milena S. Detzel ◽  
Regina Graf ◽  
...  
Keyword(s):  
Experimental Approach ◽  
Respiratory Tract Disease ◽  
Host Cell Proteins ◽  
Clinical Biomarkers ◽  
Linking Elements ◽  
Potential Link ◽  
Experimental Approaches ◽  
The Common ◽  
Tract Disease ◽  
Related Proteins

Abstract The SARS-CoV-2 outbreak has been declared a worldwide pandemic in 2020. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two computational-experimental approaches that aim at analyzing a potential link between heme-related and COVID-19 pathophysiologies. Herein, we performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Focus was laid on inflammatory pathways and distinct biomarkers as the linking elements. In a second approach, four COVID-19-related proteins, the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were computationally analyzed as potential heme-binding proteins with an experimental validation. The results contribute to the understanding of the progression of COVID-19 infections in patients with different clinical backgrounds and might allow for a more individual diagnosis and therapy in the future.

scholarly journals Linking COVID-19 and Heme-Driven Pathophysiologies: A Combined Computational–Experimental Approach

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 644
Author(s):  
Marie-Thérèse Hopp ◽  
Daniel Domingo-Fernández ◽  
Yojana Gadiya ◽  
Milena S. Detzel ◽  
Regina Graf ◽  
...  
Keyword(s):  
Experimental Approach ◽  
Respiratory Tract Disease ◽  
Host Cell Proteins ◽  
Clinical Biomarkers ◽  
Linking Elements ◽  
Potential Link ◽  
Experimental Approaches ◽  
The Common ◽  
Tract Disease ◽  
Related Proteins

The SARS-CoV-2 outbreak was declared a worldwide pandemic in 2020. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes in clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two computational–experimental approaches aimed at analyzing a potential link between heme-related and COVID-19 pathophysiologies. Herein, we performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Focus was laid on inflammatory pathways and distinct biomarkers as the linking elements. In a second approach, four COVID-19-related proteins, the host cell proteins ACE2 and TMPRSS2 as well as the viral proteins 7a and S protein were computationally analyzed as potential heme-binding proteins with an experimental validation. The results contribute to the understanding of the progression of COVID-19 infections in patients with different clinical backgrounds and may allow for a more individual diagnosis and therapy in the future.

scholarly journals Unravelling the debate on heme effects in COVID-19 infections

2020 ◽  
Author(s):  
Marie-Thérèse Hopp ◽  
Daniel Domingo-Fernández ◽  
Yojana Gadiya ◽  
Milena S. Detzel ◽  
Benjamin F. Schmalohr ◽  
...  
Keyword(s):  
Treatment Options ◽  
Respiratory Tract Disease ◽  
Host Cell Proteins ◽  
Clinical Biomarkers ◽  
Linking Elements ◽  
Potential Link ◽  
The Common ◽  
Knowledge Graphs ◽  
Tract Disease ◽  
Related Proteins

AbstractThe SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 pathogenesis. Four COVID-19 related proteins, i.e. the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options.

scholarly journals Construction and Characterization of a Recombinant Human Respiratory Syncytial Virus Encoding Enhanced Green Fluorescence Protein for Antiviral Drug Screening Assay

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Min Xu ◽  
Yue-Ying Jiao ◽  
Yuan-Hui Fu ◽  
Nan Jiang ◽  
Yuan-Bo Zheng ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Drug Screening ◽  
Green Fluorescence Protein ◽  
Respiratory Tract Disease ◽  
Green Fluorescence ◽  
Enhanced Green Fluorescence Protein ◽  
Fluorescence Protein ◽  
Syncytial Virus ◽  
Tract Disease

Human respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract disease in infants and young children and a major viral agent responsible for respiratory tract disease in immunosuppressed individuals and the elderly, but no vaccines and antiviral drugs are available. Herein the recombinant RSV (rRSV) encoding enhanced green fluorescence protein (EGFP, rRSV-EGFP) was constructed and the potential for screening anti-RSV drugs was investigated. The recombinant plasmid of pBRATm-rRSV-EGFP, containing T7 transcription cassette composed of T7 promoter, RSV antigenomic cDNA with EGFP gene, HDV ribozyme (δ), and T7 terminator in the order of 5′ to 3′, was constructed and cotransfected into BHK/T7-9 cells together with helper plasmids encoding N, P, L, and M2-1 gene, respectively. The rescued rRSV-EGFP was confirmed by increasing expression of EGFP over blind passages and by RT-PCR. rRSV-EGFP was comparable to the other two recombinant RSVs encoding red fluorescent protein (RFP, rRSV-RFP) or luciferase (Luc, rRSV-Luc) in the growth kinetic, and there was a difference in sensitivity between them for screening anti-RSV agents based on infection of HEp-2 cells. The EGFP-encoding rRSV has been constructed and rescued successfully and has the potential for high-throughput anti-RSV drug screening in vitro.

Clinical Characteristics of the Afebrile Pneumonia Associated With Chlamydia trachomatis Infection in Infants Less Than 6 Months of Age

PEDIATRICS ◽  
1979 ◽  
Vol 63 (2) ◽  
pp. 192-197
Author(s):  
Margaret A. Tipple ◽  
Marc O. Beem ◽  
Evelyn M. Saxon
Keyword(s):  
Chlamydia Trachomatis ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Clinical Characteristics ◽  
Respiratory Tract Disease ◽  
Chlamydia Trachomatis Infection ◽  
Lower Respiratory Tract Disease ◽  
Tract Disease ◽  
Blood Eosinophils ◽  
Respiratory Tract Colonization

Respiratory tract colonization with Chlamydia trachomatis commonly occurs in natally acquired chlamydial infection and is sometimes associated with a chronic, afebrile pneumonia that has relatively distinctive clinical characteristics. To further define the frequency and clinical characteristics of lower respiratory tract disease associated with C trachomatis, we grouped 56 infants aged less than 6 months with afebrile pneumonia according to nasopharyngeal shedding of Chlamydia and viruses and compared their illnesses. Forty-one (73%) were positive for C trachomatis (23 had C trachomatis only, while 18 had C trachomatis plus a virus [cytomegalovirus, respiratory synctial virus, adenovirus, rhinovirus, or enterovirus]), and 15 were C trachomatis negative (nine had a virus only, and six had neither C trachomatis nor virus). The 41 infants with C trachomatis alone or C trachomatis plus a virus were similar clinically and differed significantly from other infants in several ways: (1) onset of symptoms before 8 weeks of age; (2) gradually worsening symptoms; (3) presentation for care at 4 to 11 weeks of age; (4) presence of conjunctivitis and ear abnormalities; (5) chest roentgenograms showing bilateral, symmetrical, interstitial infiltrates and hyperexpansion; (6) peripheral blood eosinophils ≥300/cu mm; and (7) elevated values for serum immunoglobulins M, G, and A.

Sign in / Sign up

Export Citation Format

Share Document