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

Abstract

Please cite this article in press as: Durdagi et al., The neutralization effect of montelukaston SARS-CoV-2 is shown by multiscale in silicosimulations and combined in vitro studies, Molecular Therapy (2021),

The Petasites hybridus CO2 Extract (Ze 339) Blocks SARS-CoV-2 Replication In Vitro

“…In our current study, a pre-incubation of cells with the test compounds for 2 h prior to virus infection had a clear positive effect, suggesting a possible prophylactic role also for the petasins. While the montelukast IC 50 values were at 18.82 µM and 25 µM in in vitro cell culture models of SARS-CoV-2 activity [73,74], the IC 50 s for Ze 339, isopetasin, and neopetasin determined in the current study were significantly lower. The visibly shallower inhibition curves of the petasin compounds compared to the antiviral mechanism of remdesivir could suggest a more complex mode of interference with the viral life cycle which is supported by the abovementioned various mechanisms of action of Ze 339.…”

“…It is also worth mentioning that the mechanism of anti-inflammatory action of Ze 339 is comparable to that of montelukast and zileuton, which are currently under discussion as therapeutic candidates for the treatment of COVID-19 [25][26][27][28][29]. A recent study by Durdagi et al [73] demonstrated that the neutralization effect of montelukast on SARS-CoV-2 in vitro suggests that virus replication could be significantly delayed. The authors suggested to consider montelukast for prophylactic treatment.…”

The Petasites hybridus CO2-extract (Ze 339) blocks SARS-CoV-2 replication in vitro

“…In our current study, a pre-incubation of cells with the test compounds for 2 h prior to virus infection had a clear positive effect, suggesting a possible prophylactic role also for the petasins. While the montelukast IC 50 values were at 18.82 μM and 25 μM in in vitro cell culture models of SARS-CoV-2 activity [73, 74], the IC 50 s for Ze 339, isopetasin and neopetasin determined in the current study were significantly lower. The visibly shallower inhibition curves of the petasin compounds compared to the antiviral mechanism of remdesivir could suggest a more complex mode of interference with the viral life cycle which is supported by the above mentioned various mechanisms of action of Ze 339.…”

“…It is further worth mentioning that the mechanism of anti-inflammatory action of Ze 339 is comparable to that of montelukast and zileuton, which are currently under discussion as therapeutic candidates for the treatment of COVID-19 [25-29]. In a recent study by Durdagi et al [73] demonstrated the neutralization effect of montelukast on SARS-CoV-2 in vitro by showing that virus replication could be significantly delayed. The authors suggested to consider montelukast for prophylactic treatment.…”

Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography

“…After crystals of size 1-5 μm × 5-10 μm × 10-20 μm reached, they were soaked with 100 μg/mL of drug solution by mixing the drug solutions into protein crystal solution for both constructs. Promising drug candidates were chosen by intensive literature search: Lopinavir [22], Rosuvastatin and Atorvastatin [23], Adefovir [24], Umifenovir [25], Empagliflozin [26], Ebselen [17], Montelukast [27,28].…”