Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/37151
Title: Preliminary virtual screening studies to identify grp78 inhibitors which may interfere with sars-cov-2 infection
Authors: Palmeira, A.
Sousa, E.
Köseler, Aylin
Sabirli, R.
Gören, Tarık
Türkçüer, İ.
Kurt, Ö.
Keywords: Antiviral
Covid-19
Gene expression
GRP78
Repurposed drugs
SARS-CoV-2
Virtual screening
bafetinib
danusertib
dasatinib
glucose regulated protein 78 inhibitor
imatinib
nilotinib
protein inhibitor
unclassified drug
adult
aged
antiviral activity
Article
blood analysis
clinical article
controlled study
coronavirus disease 2019
drug protein binding
drug screening
drug structure
female
gene expression regulation
gene targeting
GRP78 gene
human
male
molecular docking
pneumonia
structure activity relation
upregulation
virus gene
Publisher: MDPI AG
Abstract: 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
URI: https://hdl.handle.net/11499/37151
https://doi.org/10.3390/ph13060132
ISSN: 1424-8247
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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