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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2)

ORF8 (1)

ProteinS1 (1)


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    In vitro screening of herbal medicinal products for their supportive curing potential in the context of SARS-CoV-2

    Authors: Hoai Tran; Philipp Peterburs; Jan Seibel; Dimitri Abramov-Sommariva; Evelyn Lamy

    doi:10.1101/2021.03.01.433344 Date: 2021-03-01 Source: bioRxiv

    Background: Herbal medicinal products have a long-standing history of use in the therapy of common respiratory infections MESHD. In the COVID-19 pandemic MESHD, they may have the potential for symptom relief in non-severe or moderate disease cases. Here we describe the results derived by in vitro screening of five herbal medicinal products with regard to their potential to i) interfere with the binding of the human Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor with the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN S1 protein PROTEIN, ii) modulate the release of the human defensin HBD1 and cathelicidin LL-37 HGNC from human A549 lung cells upon Spike S1 protein PROTEIN stimulation and iii) modulate the release of IFN-{gamma HGNC} from activated human peripheral blood mononuclear cells (PBMC). The investigated extracts were: Sinupret extract (SINx), Bronchipret thyme-ivy (BRO TE), Bronchipret thyme-primrose (BRO TP), Imupret (IMU), and Tonsipret (TOP). Methods: The inhibitory effect of the herbal medicinal products on the binding interaction of Spike S1 protein PROTEIN and the human ACE2 receptor was measured by ELISA. The effects on intracellular IFN-{gamma HGNC} expression in stimulated human PBMCs were measured by flow cytometry. Regulation on HBD1 HGNC and LL-37 HGNC expression and secretion was assessed in 25d long-term cultured human lung A549 epithelial cells by RT-PCR and ELISA. Results: IMU and BRO TE concentration-dependently inhibited the interaction between spike protein PROTEIN and the ACE2 HGNC Receptor. However, this effect was only observed in the cell-free assay at a concentration range which was later on determined as cytotoxic to human PBMC. SINx, TOP and BRO TP significantly upregulated the intracellular expression of antiviral IFN{gamma HGNC} from stimulated PBMC. Co-treatment of A549 cells with IMU or BRO TP together with SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN protein significantly upregulated mRNA expression (IMU) and release (IMU and BRO TP) of HBD1 HGNC and LL-37 HGNC (BRO TP). Conclusions: The in vitro screening results provide first evidence for an immune activating potential of some of the tested herbal medicinal extracts in the context of SARS-CoV-2. Whether these could be helpful in prevention of SARS-CoV-2 invasion MESHD or supportive in recovery from SARS-CoV-2 infection MESHD needs deeper understanding of the observations.

    LL-37 HGNC fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 HGNC Inhibits Binding of SARS-CoV-2 Spike PROTEIN Protein to its Cellular Receptor Angiotensin Converting Enzyme 2 HGNC In Vitro

    Authors: Annika Roth; Steffen Luetke; Denise Meinberger; Gabriele Hermes; Gerhard Sengle; Manuel Koch; Thomas Streichert; Andreas R. Klatt; Maarja Andaloussi Mae; Lars Muhl; Nicky M. Craig; Samantha J. Griffiths; Jurgen G. Haas; Christine Tait Burkard; Urban Lendahl; Graeme M. Birdsey; Christer Betsholtz; Michela Noseda; Andrew Baker; Anna M Randi; Sofia Palma; Carolina Escobar; Josefina bascunan; Rodrigo Munoz; Monica Pinto; Daniela Cardemil; Marcelo Navarrete; Soledad Reyes; Victoria Espinoza; Nicolas Yanez; Christian Caglevic

    doi:10.1101/2020.12.02.408153 Date: 2020-12-02 Source: bioRxiv

    Objective: Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the pathogen accountable for the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Viral entry via binding of the receptor binding domain (RBD) located within the S1 subunit of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN ( S) protein PROTEIN to its target receptor angiotensin converting enzyme (ACE) 2 HGNC is a key step in cell infection. The efficient transition of the virus is linked to a unique protein called open reading frame ( ORF MESHD) 8. As SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs can develop into life threatening lower respiratory syndromes, effective therapy options are urgently needed. Several publications propose vitamin D treatment, although its mode of action against COVID-19 MESHD is not fully elucidated. It is speculated that vitamin D's beneficial effects are mediated by up regulating LL-37 HGNC, a well known antimicrobial peptide with antiviral effects. Methods: Recombinantly expressed SARS-CoV-2 S protein PROTEIN, the extended S1 subunit (S1e), the S2 subunit (S2), the receptor binding domain (RBD), and ORF8 PROTEIN were used for surface plasmon resonance ( SPR HGNC) studies to investigate LL-37 HGNC's ability to bind to SARS-CoV-2 proteins MESHD and to localize its binding site within the S protein PROTEIN. Binding competition studies were conducted to confirm an inhibitory action of LL-37 HGNC on the attachment of SARS-CoV-2 S MESHD S protein PROTEIN to its entry receptor ACE2 HGNC. Results: We could show that LL-37 HGNC binds to SARS-CoV-2 S MESHD S protein PROTEIN ( LL-37 HGNC/S-Strep KD = 407 nM, LL-37 HGNC/S-His KD = 414 nM) with the same affinity, as SARS-CoV-2 binds to hACE2 HGNC ( hACE2 HGNC/S-Strep KD = 374 nM, hACE2 HGNC/S-His KD = 368 nM). The binding is not restricted to the RBD of the S protein PROTEIN, but rather distributed along the entire length of the protein. Interaction between LL-37 HGNC and ORF8 PROTEIN was detected with a KD of 294 nM. Further, inhibition of the binding of S-Strep (IC50 = 735 nM), S1e (IC50 = 168 nM), and RBD (IC50 = 126 nM) to hACE2 HGNC by LL-37 HGNC was demonstrated. Conclusions: We have revealed a biochemical link between vitamin D, LL-37 HGNC, and COVID-19 MESHD severity. SPR HGNC analysis demonstrated that LL-37 HGNC binds to SARS-CoV-2 S MESHD S protein PROTEIN and inhibits binding to its receptor hACE2 HGNC, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 HGNC that protects from SARS-CoV-2 infection MESHD, and the therapeutic administration of vitamin D for the treatment of COVID-19 MESHD patients. Further, our results provide evidence that the direct use of LL-37 HGNC by inhalation and systemic application may reduce the severity of COVID-19 MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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