Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

There are no transmission terms in the subcorpus


Seroprevalence

There are no seroprevalence terms in the subcorpus

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    The Anti-histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits SARS-CoV-2 Infection MESHD in Reconstituted Human Nasal Tissue In Vitro

    Authors: Robert Konrat; Henrietta Papp; Valeria Szijarto; Tanja Gesell; Gabor Nagy; Monika Madai; Safia Zeghbib; Anett Kuczmog; Zsofia Lanszki; Zsuzsanna Helyes; Gabor Kemenesi; Ferenc Jakab; Eszter Nagy; Michel C. Nussenzweig; Timothy P. Sheahan; Pinaki Banerjee; Ye Li; Sufang Li; Luciana Melo Garcia; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani

    doi:10.1101/2020.09.15.296228 Date: 2020-09-15 Source: bioRxiv

    Background: The COVID-19 pandemic is an enormous threat for healthcare systems and economies worldwide that urgently demands effective preventive and therapeutic strategies. Unlike the development of vaccines and new drugs specifically targeting SARS-CoV-2, repurposing of approved or clinically tested drugs can provide an immediate solution. Methods: We applied a novel computational approach to search among approved and clinically tested drugs from the DrugBank database. Candidates were selected based on Shannon entropy homology and predefined activity profiles of three small molecules with proven anti-SARS-CoV activity and a published data set. Antiviral activity of a predicted drug, azelastine, was tested in vitro in SARS-CoV-2 infection MESHD assays with Vero E6 monkey kidney epithelial cells and reconstituted human nasal tissue. The effect on viral replication was assessed by quantification of viral genomes by droplet digital PCR. Findings: The computational approach with four independent queries identified major drug families, most often and in overlapping fashion anti-infective, anti-inflammatory, anti- hypertensive MESHD, anti-histamine and neuroactive drugs. Azelastine, an histamine 1 receptor-blocker, was predicted in multiple screens, and based on its attractive safety profile and availability in nasal formulation, was selected for experimental testing. Azelastine significantly reduced cytopathic effect and SARS-CoV-2 infection MESHD of Vero E6 cells with an EC50 of ~6 M both in a preventive and treatment setting. Furthermore, azelastine in a commercially available nasal spray tested at 5-fold dilution was highly potent in inhibiting viral propagation in SARS-CoV-2 infected MESHD reconstituted human nasal tissue. Interpretations: Azelastine, an anti-histamine, available in nasal sprays developed against allergic rhinitis HP allergic rhinitis MESHD may be considered as a topical prevention or treatment of nasal colonization with SARS-CoV-2. As such, it could be useful in reducing viral spread and prophylaxis of COVID-19. Ultimately, its potential benefit should be proven in clinical studies. Funding: provided by the Hungarian government to the National Laboratory of Virology and by CEBINA GmbH.

    Expression of ACE2, TMPRSS2, and CTSL in human airway epithelial cells under physiological and pathological conditions: Implications for SARS-CoV2 infection MESHD

    Authors: Junping Yin; Brigitte Kasper; Frank Petersen; Xinhua Yu

    doi:10.1101/2020.08.06.240796 Date: 2020-08-07 Source: bioRxiv

    SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry-related genes in primary human airway epithelial cells isolated from donors with different physiological and pathological backgrounds such as smoking, COPD MESHD, asthma HP asthma MESHD, lung cancer, allergic rhinitis HP allergic rhinitis MESHD, cystic fibrosis MESHD, or viral infections MESHD. By reanalyzing 54 GEO datasets comprising transcriptomic data of 3428 samples, this study revealed that i) smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; ii) infection of rhinovirus as well as poly(I:C) stimulation leads to high expression of all three SARS-CoV-2 entry-related genes; iii) expression of ACE2 and cathepsin L in nasal epithelial cells are decreased in patients with asthma HP and allergic rhinitis HP. In conclusion, this study implicates that infection of respiratory viruses, cigarette smoking and allergic respiratory diseases MESHD might affect the susceptibility to and the development of COVID-19.

    Effect of Dietary Modification for Targeting Histamine Activity in Patients of Allergic Rhinitis HP Allergic Rhinitis MESHD: a Randomised Open Label Study

    Authors: Mohsin Ali Khan; Zaw Ali Khan; Abdul Naeem; Nigar Naqvi; Shikha Srivastava; Anuja Bhargava; Rajeev Krishna Gupta

    doi:10.21203/rs.3.rs-25717/v1 Date: 2020-04-27 Source: ResearchSquare

    Allergic Rhinitis HP Allergic Rhinitis MESHD refers to immunoglobulin E mediated inflammation MESHD of the nasal cavity. Mast cell activation releases histamine, the inflammatory mediator that plays a central role in the biochemical mechanism of this disease. It is metabolised by Diamine Oxidase (DAO) and Histamine N-methyltransferase (HNMT). In this randomised open label study, we recruited 60 patients out of which 30 patients were provided standard treatment and 30 were provided standard treatment along with instructions for dietary modification. The dietary modification consisted of excluding commonly consumed histamine-rich foods and foods containing pro-histamine or anti-DAO active constituents. Each patient was followed up 3 times over the course of 15 days. The patients in the dietary modification group showed significant improvement in rhinitis HP rhinitis MESHD symptoms within 7 days, while the control group’s improvement was not significant in the same amount of time. The overall improvement between the first and last visits was more significant in the dietary modification group as compared to the control group. Thus, the exclusion of histamine-rich foods and foods containing pro-histamine or anti-DAO compounds may be recommended to patients of allergic rhinitis HP allergic rhinitis MESHD for quicker and better recovery. This approach may also be explored in other conditions where histamine is implicated such as asthma HP asthma MESHD and infections caused by coronaviruses.

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MeSH Disease
Human Phenotype
Transmission
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