Publications by authors named "Reynir Scheving"

6 Publications

  • Page 1 of 1

Inactivation of SARS-CoV-2 and HCoV-229E in vitro by ColdZyme® a medical device mouth spray against the common cold.

J Med Virol 2021 03 14;93(3):1792-1795. Epub 2020 Oct 14.

Zymetech, Reykjavík, Iceland.

Background: The coronavirus disease 2019 (COVID-19) pandemic calls for effective and safe treatments. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 actively replicates in the throat, unlike SARS-CoV, and shows high pharyngeal viral shedding even in patients with mild symptoms of the disease. HCoV-229E is one of four coronaviruses causing the common cold. In this study, the efficacy of ColdZyme® (CZ-MD), a medical device mouth spray, was tested against SARS-CoV-2 and HCoV-229E in vitro. The CZ-MD provides a protective glycerol barrier containing cod trypsin as an ancillary component. Combined, these ingredients can inactivate common cold viruses in the throat and mouth. The CZ-MD is believed to act on the viral surface proteins that would perturb their entry pathway into cells. The efficacy and safety of the CZ-MD have been demonstrated in clinical trials on the common cold.

Method Of Study: The ability of the CZ-MD to inactivate SARS-CoV-2 and HCoV-229E was tested using an in vitro virucidal suspension test (ASTM E1052).

Results: CZ-MD inactivated SARS-CoV-2 by 98.3% and HCoV-229E by 99.9%.

Conclusion: CZ-MD mouth spray can inactivate the respiratory coronaviruses SARS-CoV-2 and HCoV-229E in vitro. Although the in vitro results presented cannot be directly translated into clinical efficacy, the study indicates that CZ-MD might offer a protective barrier against SARS-CoV-2 and a decreased risk of COVID-19 transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537187PMC
March 2021

Biochemical characterization of a native group III trypsin ZT from Atlantic cod (Gadus morhua).

Int J Biol Macromol 2019 Mar 12;125:847-855. Epub 2018 Dec 12.

Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland. University of Iceland, Sæmundargata 2, 101 Reykjavik, Iceland. Electronic address:

Atlantic cod trypsin ZT is biochemically characterized for the first time in this report in comparison to a group I trypsin (cod trypsin I). To our knowledge, trypsin ZT is the first thoroughly characterized group III trypsin. A more detailed understanding of trypsin ZT biochemistry may give insight into its physiological role as well as its potential use within the biotechnology sector. Stability is an important factor when it comes to practical applications of enzymes. Compared to trypsin I, trypsin ZT shows differences in pH and heat stability, sensitivity to inhibitors and sub-site substrate specificity as shown by multiplex substrate profiling analysis. Based on the analysis, trypsin ZT cleaved at arginine and lysine as other trypsins. Furthermore, trypsin ZT is better than trypsin I in cleaving peptides containing several consecutive positively charged residues. Lysine- and arginine-rich amino acid sequences are frequently found in human viral proteins. Thus, trypsin ZT may be effective in inactivating human and fish viruses implying a possible role for the enzyme in the natural defence of Atlantic cod. The results from this study can lead to multiple practical applications of trypsin ZT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2018.12.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112495PMC
March 2019

Nitric oxide contributes to protein homeostasis by S-nitrosylations of the chaperone HSPA8 and the ubiquitin ligase UBE2D.

Redox Biol 2019 01 16;20:217-235. Epub 2018 Oct 16.

Institute for Clinical Pharmacology, Goethe-University Hospital, 60590 Frankfurt am Main, Germany. Electronic address:

Upregulations of neuronal nitric oxide synthase (nNOS) in the rodent brain have been associated with neuronal aging. To address underlying mechanisms we generated SH-SY5Y neuronal cells constitutively expressing nNOS at a level similar to mouse brain (nNOS+ versus MOCK). Initial experiments revealed S-nitrosylations (SNO) of key players of protein homeostasis: heat shock cognate HSC70/HSPA8 within its nucleotide-binding site, and UBE2D ubiquitin conjugating enzymes at the catalytic site cysteine. HSPA8 is involved in protein folding, organelle import/export and chaperone-mediated LAMP2a-dependent autophagy (CMA). A set of deep redox and full proteome analyses, plus analysis of autophagy, CMA and ubiquitination with rapamycin and starvation as stimuli confirmed the initial observations and revealed a substantial increase of SNO modifications in nNOS+ cells, in particular targeting protein networks involved in protein catabolism, ubiquitination, carbohydrate metabolism and cell cycle control. Importantly, NO-independent reversible oxidations similarly occurred in both cell lines. Functionally, nNOS caused an accumulation of proteins, including CMA substrates and loss of LAMP2a. UBE2D activity and proteasome activity were impaired, resulting in dysregulations of cell cycle checkpoint proteins. The observed changes of protein degradation pathways caused an expansion of the cytoplasm, large lysosomes, slowing of the cell cycle and suppression of proliferation suggesting a switch of the phenotype towards aging, supported by downregulations of neuronal progenitor markers but increase of senescence-associated proteins. Hence, upregulation of nNOS in neuronal cells imposes aging by SNOing of key players of ubiquitination, chaperones and of substrate proteins leading to interference with crucial steps of protein homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2018.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202877PMC
January 2019

Rab7-a novel redox target that modulates inflammatory pain processing.

Pain 2017 07;158(7):1354-1365

Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.

Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000000920DOI Listing
July 2017

Protein S-nitrosylation and denitrosylation in the mouse spinal cord upon injury of the sciatic nerve.

J Proteomics 2012 Jul 14;75(13):3987-4004. Epub 2012 May 14.

Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, 60590 Frankfurt am Main, Germany.

Nitric oxide is a pain signaling molecule and exerts its influence through two primary pathways: by stimulation of soluble guanylylcyclase and by direct S-nitrosylation (SNO) of target proteins. We assessed in the spinal cord the SNO-proteome with two methods, two-dimensional S-nitrosothiol difference gel electrophoresis (2D SNO-DIGE) and SNO-site identification (SNOSID) at baseline and 24h after sciatic nerve injury with/without pretreatment with the nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). After nerve injury, SNO-DIGE revealed 30 proteins with increased and 23 proteins with decreased S-nitrosylation. SNO-sites were identified for 17 proteins. After sham surgery only 3 proteins were up-nitrosylated. L-NAME pretreatment substantially reduced both constitutive and nerve injury evoked up-S-nitrosylation. For the top candidates S-nitrosylation was confirmed with the biotin switch technique and time course analyses at 1 and 7days showed that SNO modifications of protein disulfide isomerase, glutathione synthase and peroxiredoxin-6 had returned to baseline within 7days whereas S-nitrosylation of mitochondrial aconitase 2 was further increased. The identified SNO modified proteins are involved in mitochondrial function, protein folding and transport, synaptic signaling and redox control. The data show that nitric oxide mediated S-nitrosylation contributes to the nerve injury-evoked pathology in nociceptive signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2012.05.006DOI Listing
July 2012

SNO-ing at the nociceptive synapse?

Pharmacol Rev 2011 Jun 24;63(2):366-89. Epub 2011 Mar 24.

Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, Haus 74; 60590 Frankfurt am Main, Germany.

Nitric oxide is generally considered a pronociceptive retrograde transmitter that, by activation of soluble guanylyl cyclase-mediated cGMP production and activation of cGMP-dependent protein kinase, drives nociceptive hypersensitivity. The duality of its functions, however, is increasingly recognized. This review summarizes nitric-oxide-mediated direct S-nitrosylation of target proteins that may modify nociceptive signaling, including glutamate receptors and G-protein-coupled receptors, transient receptor potential channels, voltage-gated channels, proinflammatory enzymes, transcription factors, and redoxins. S-Nitrosylation events require close proximity of nitric oxide production and target proteins and a permissive redox state in the vicinity. Despite the diversity of potential targets and effects, three major schemes arise that may affect nociceptive signaling: 1) S-Nitrosylation-mediated changes of ion channel gating properties, 2) modulation of membrane fusion and fission, and thereby receptor and channel membrane insertion, and 3) modulation of ubiquitination, and thereby protein degradation or transcriptional activity. In addition, S-Nitrosylation may alter the production of nitric oxide itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/pr.110.004200DOI Listing
June 2011
-->