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

• DOI: 10.1016/j.ymthe.2021.10.014
• Publication Date: 2021-10-22T04:00:24Z
• Authors: Serdar Durdagi; Timucin Avsar; Muge Didem Orhan; Muge Serhatli; Bertan Koray Balc...; Hasan Umit Ozturk; Alisan Kayabolen; Yuksel Cetin; Seyma Aydinlik; Tugba Bagci-Onder; Saban Tekin; Hasan Demirci; Mustafa Guzel; Atilla Akdemir; Seyma Calis; Lalehan Oktay; Ilayda Tolu; Yasar Enes Butun; Ece Erdemoglu; Alpsu Olkan; Nurettin Tokay; Şeyma Işık; Aysenur Ozcan; Elif Acar; Sehriban Buyukkilic; Yesim Yumak
• Keywords: 2019-20 coronavirus outbreak

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In current drug repurposing study, we identified leukotriene (D4) receptor antagonist montelukast a novel agent that simultaneously targets two important SARS-CoV-2. We initially demonstrated dual inhibition profile through multiscale molecular modeling studies. Next, characterized its effect on both by vitro experiments including enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization HEK293T/hACE2+TMPRSS2, and virus assay using xCELLigence MP real-time cell analyzer. Our integrated silico results confirmed potential main protease entry into host (spike/ACE2). The showed SARS-CoV-2 activity was delayed with for 20 h infected cells. rapid use new small molecules pandemic is very today. Montelukast, whose pharmacokinetic pharmacodynamic properties are well has widely used asthma since 1998, should urgently be completed clinical phase and, if proved studies, it against coronavirus disease 2019 (COVID-19).