The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Basit Öğe Kaydı
dc.authorid0000-0002-1423-0435
dc.contributor.authorDurdağı, Serdar
dc.contributor.authorAvşar, Timuçin
dc.contributor.authorOrhan, Müge Didem
dc.contributor.authorSerhatlı, Müge
dc.contributor.authorBalcıoğlu, Bertan Koray
dc.contributor.authorÖztürk, Hasan Ümit
dc.contributor.authorKayabölen, Alişan
dc.contributor.authorÇetin, Yüksel
dc.contributor.authorAydınlık, Şeyma
dc.contributor.authorBağcı-Önder, Tuğba
dc.contributor.authorTekin, Şaban
dc.contributor.authorDemirci, Hasan
dc.contributor.authorGüzel, Mustafa
dc.contributor.authorAkdemir, Atilla
dc.contributor.authorÇalış, Şeyma
dc.contributor.authorOktay, Lalehan
dc.contributor.authorTolu, İlayda
dc.contributor.authorBütün, Yaşar Enes
dc.contributor.authorErdemoğlu, Ece
dc.contributor.authorOlkan, Alpsu
dc.contributor.authorTokay, Nurettin
dc.contributor.authorIşık, Şeyma
dc.contributor.authorÖzcan, Ayşenur
dc.contributor.authorAcar, Elif
dc.contributor.authorBüyükkılıç, Şehriban
dc.contributor.authorYumak, Yeşim
dc.date.accessioned2022-02-24T11:14:22Z
dc.date.available2022-02-24T11:14:22Z
dc.date.issued2022
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.description.abstractSmall molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).
dc.description.sponsorshipScientific Research Projects Commission of Bahcesehir Universityen_US
dc.identifier.citationDurdağı, S., Avşar, T., Orhan, M. D., Serhatlı, M., Balcıoğlu, B. K., Öztürk, H. Ü. ... Yumak, Y. (2022). The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies. Molecular Therapy, 30(2), 963-974. http://doi.org/10.1016/j.ymthe.2021.10.014
dc.identifier.doi10.1016/j.ymthe.2021.10.014
dc.identifier.endpage974
dc.identifier.issn1525-0016
dc.identifier.issn1525-0024
dc.identifier.issue2
dc.identifier.pmid34678509
dc.identifier.scopus2-s2.0-85119042965
dc.identifier.scopusqualityQ1
dc.identifier.startpage963
dc.identifier.urihttp://doi.org/10.1016/j.ymthe.2021.10.014
dc.identifier.urihttps://hdl.handle.net/20.500.12511/8994
dc.identifier.volume30
dc.identifier.wos000752448900006en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorGüzel, Mustafa
dc.institutionauthorBütün, Yaşar Enes
dc.language.isoen
dc.publisherCell Press
dc.relation.ispartofMolecular Therapyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/18AG003
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectSARS-CoV-2
dc.subjectVitro Studies
dc.subjectMontelukast
dc.subjectSilico Simulations
dc.titleThe neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
Guzel-Mustafa-2022.pdf
Boyut:
1.62 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu