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Image3_The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue.jpg
| العنوان: | Image3_The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue.jpg |
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| المؤلفون: | Robert Konrat, Henrietta Papp, Janine Kimpel, Annika Rössler, Valéria Szijártó, Gábor Nagy, Mónika Madai, Safia Zeghbib, Anett Kuczmog, Zsófia Lanszki, Tanja Gesell, Zsuzsanna Helyes, Gábor Kemenesi, Ferenc Jakab, Eszter Nagy |
| سنة النشر: | 2022 |
| المجموعة: | Frontiers: Figshare |
| مصطلحات موضوعية: | Pharmacology, Basic Pharmacology, Clinical Pharmacology and Therapeutics, Clinical Pharmacy and Pharmacy Practice, Pharmaceutical Sciences, Pharmacogenomics, Toxicology (incl. Clinical Toxicology), Pharmacology and Pharmaceutical Sciences not elsewhere classified, COVID-19, computational drug repurposing, SARS-CoV-2, azelastine, anti-viral activity, variants of concern, nasal colonization |
| الوصف: | Background and purpose: The COVID-19 pandemic continues to pose challenges, especially with the emergence of new SARS-CoV-2 variants that are associated with higher infectivity and/or compromised protection afforded by the current vaccines. There is a high demand for additional preventive and therapeutic strategies effective against this changing virus. Repurposing of approved or clinically tested drugs can provide an immediate solution. Experimental Approach: We applied a novel computational approach to search among approved and commercially available drugs. Antiviral activity of a predicted drug, azelastine, was tested in vitro in SARS-CoV-2 infection assays with Vero E6 cells, Vero cells stably overexpressing the human TMPRSS2 and ACE2 proteins as well as on reconstituted human nasal tissue using the predominant variant circulating in Europe in summer 2020, B.1.177 (D614G variant), and its emerging variants of concern; B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants. The effect of azelastine on viral replication was assessed by quantification of viral genomes by droplet digital PCR or qPCR. Key results: The computational approach identified major drug families, such as anti-infective, anti-inflammatory, anti-hypertensive, antihistamine, and neuroactive drugs. Based on its attractive safety profile and availability in nasal formulation, azelastine, a histamine 1 receptor-blocker was selected for experimental testing. Azelastine reduced the virus-induced cytopathic effect and SARS-CoV-2 copy numbers both in preventive and treatment settings upon infection of Vero cells with an EC 50 of 2.2–6.5 µM. Comparable potency was observed with the alpha, beta and delta variants. Furthermore, five-fold dilution (containing 0.02% azelastine) of the commercially available nasal spray formulation was highly potent in inhibiting viral propagation in reconstituted human nasal tissue. Conclusion and Implications: Azelastine, an antihistamine available as nasal sprays developed against allergic rhinitis may be ... |
| نوع الوثيقة: | still image |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/figure/Image3_The_Anti-Histamine_Azelastine_Identified_by_Computational_Drug_Repurposing_Inhibits_Infection_by_Major_Variants_of_SARS-CoV-2_in_Cell_Cultures_and_Reconstituted_Human_Nasal_Tissue_jpg/20189732 |
| DOI: | 10.3389/fphar.2022.861295.s004 |
| الاتاحة: | https://doi.org/10.3389/fphar.2022.861295.s004 https://figshare.com/articles/figure/Image3_The_Anti-Histamine_Azelastine_Identified_by_Computational_Drug_Repurposing_Inhibits_Infection_by_Major_Variants_of_SARS-CoV-2_in_Cell_Cultures_and_Reconstituted_Human_Nasal_Tissue_jpg/20189732 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.3E7DE9F3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fphar.2022.861295.s004 |
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