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The neutralization effect of montelukaston SARS-CoV-2 is shown by multiscale in silicosimulations and combined in vitro studies

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dc.contributor.authorDurdagi, Serdar
dc.contributor.authorAvsar, Timucin
dc.contributor.authorOrhan, Muge Didem
dc.contributor.authorSerhatli, Muge
dc.contributor.authorBalcioglu, Bertan Koray
dc.contributor.authorOzturk, Hasan Umit
dc.contributor.authorKayabolen, Alisan
dc.contributor.authorCetin, Yuksel
dc.contributor.authorAydinlik, Seyma
dc.contributor.authorBagci-Onder, Tugba
dc.contributor.authorTekin, Saban
dc.contributor.authorDemirci, Hasan
dc.contributor.authorGuzel, Mustafa
dc.contributor.authorAkdemir, ATİLLA
dc.contributor.authorCalis, Seyma
dc.contributor.authorOktay, Lalehan
dc.contributor.authorTolu, Ilayda
dc.contributor.authorButun, Yasar Enes
dc.contributor.authorErdemoglu, Ece
dc.contributor.authorOlkan, Alpsu
dc.contributor.authorTokay, Nurettin
dc.contributor.authorIşık, Şeyma
dc.contributor.authorOzcan, Aysenur
dc.contributor.authorAcar, Elif
dc.contributor.authorBuyukkilic, Sehriban
dc.contributor.authorYumak, Yesim
dc.contributor.institutionauthorAKDEMİR, ATİLLA
dc.date.accessioned2022-01-07T21:00:00Z
dc.date.available2022-01-07T21:00:00Z
dc.date.issued2021-10-19T00:00:00Z
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.identifier.doi10.1016/j.ymthe.2021.10.014
dc.identifier.pubmed34678509
dc.identifier.scopus85119042965
dc.identifier.urihttp://hdl.handle.net/20.500.12645/30044
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCOVID-19
dc.subjectMD simulations
dc.subjectdrug repurposing
dc.subjectmolecular docking
dc.subjectmontelukast
dc.subjectpseudovirus neutralization
dc.subjectvirus neutralization
dc.titleThe neutralization effect of montelukaston SARS-CoV-2 is shown by multiscale in silicosimulations and combined in vitro studies
dc.typeArticle
dspace.entity.typePublication
local.avesis.id91e55197-6b3e-4446-a3b3-a96866e039f5
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
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relation.isAuthorOfPublication.latestForDiscovery19bc513a-c695-4e72-ba1d-83b8d6c574c8
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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