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Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection

SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patien...

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Autores principales: Palmeira, Andreia, Sousa, Emília, Köseler, Aylin, Sabirli, Ramazan, Gören, Tarık, Türkçüer, İbrahim, Kurt, Özgür, Pinto, Madalena M., Vasconcelos, M. Helena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345920/
https://www.ncbi.nlm.nih.gov/pubmed/32630514
http://dx.doi.org/10.3390/ph13060132
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author Palmeira, Andreia
Sousa, Emília
Köseler, Aylin
Sabirli, Ramazan
Gören, Tarık
Türkçüer, İbrahim
Kurt, Özgür
Pinto, Madalena M.
Vasconcelos, M. Helena
author_facet Palmeira, Andreia
Sousa, Emília
Köseler, Aylin
Sabirli, Ramazan
Gören, Tarık
Türkçüer, İbrahim
Kurt, Özgür
Pinto, Madalena M.
Vasconcelos, M. Helena
author_sort Palmeira, Andreia
collection PubMed
description SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.
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spelling pubmed-73459202020-07-09 Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection Palmeira, Andreia Sousa, Emília Köseler, Aylin Sabirli, Ramazan Gören, Tarık Türkçüer, İbrahim Kurt, Özgür Pinto, Madalena M. Vasconcelos, M. Helena Pharmaceuticals (Basel) Communication SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity. MDPI 2020-06-25 /pmc/articles/PMC7345920/ /pubmed/32630514 http://dx.doi.org/10.3390/ph13060132 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Palmeira, Andreia
Sousa, Emília
Köseler, Aylin
Sabirli, Ramazan
Gören, Tarık
Türkçüer, İbrahim
Kurt, Özgür
Pinto, Madalena M.
Vasconcelos, M. Helena
Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title_full Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title_fullStr Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title_full_unstemmed Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title_short Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
title_sort preliminary virtual screening studies to identify grp78 inhibitors which may interfere with sars-cov-2 infection
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345920/
https://www.ncbi.nlm.nih.gov/pubmed/32630514
http://dx.doi.org/10.3390/ph13060132
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