A Case for Montelukast in COVID-19: "The use of Computational Docking to estimate the effects of Montelukast on potential viral main protease catalytic site"

Mansoor, Salman; Saadat, Shoab; Amin, Aitzaz; Ali, Ihsan; Ghaffar, Muhammad Tauseef; Amin, Usman; Mukhtar, Mohsin

doi:10.21203/rs.3.rs-27079/v1

Cited by 5 publications

(6 citation statements)

References 23 publications

(29 reference statements)

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“…Therefore, it was hypothesized that montelukast may also have antiviral activity against SARS-CoV-2 [27]. Studies related to SARS-CoV-2-montelukast interaction are mostly in silico - [44,45,46] and in vitro - [17,42] oriented. Accordingly, we suggest that although montelukast interacts with Mpro, it may interfere through an allosteric effect, disrupting its conformation and perturbing the crystal lattice contacts.…”

Section: Discussionmentioning

confidence: 99%

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

Güven

Gul

Ayan

et al. 2021

Preprint

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Since early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in-silico drug screening studies has been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple structures soaked with 9 drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.

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Section: Discussionmentioning

confidence: 99%

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

Güven

Gul

Ayan

et al. 2021

Preprint

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“…Montelukast has been shown to inhibit at least one other protease, eosinophil protease ( Langlois et al, 2006 ). Mansoor and colleagues deduced that it may bind to M pro on the basis of a simple molecular docking study ( Mansoor et al, 2020 ). Wu et al also reported putative binding of montelukast to M pro in a computational study using the same Internal Coordinate Mechanics modeling methods ( Wu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Computational Repurposing of Drugs and Natural Products Against SARS-CoV-2 Main Protease (Mpro) as Potential COVID-19 Therapies

Piplani

Singh

Petrovsky

et al. 2022

Front. Mol. Biosci.

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We urgently need to identify drugs to treat patients suffering from COVID-19 infection. Drugs rarely act at single molecular targets. Off-target effects are responsible for undesirable side effects and beneficial synergy between targets for specific illnesses. They have provided blockbuster drugs, e.g., Viagra for erectile dysfunction and Minoxidil for male pattern baldness. Existing drugs, those in clinical trials, and approved natural products constitute a rich resource of therapeutic agents that can be quickly repurposed, as they have already been assessed for safety in man. A key question is how to screen such compounds rapidly and efficiently for activity against new pandemic pathogens such as SARS-CoV-2. Here, we show how a fast and robust computational process can be used to screen large libraries of drugs and natural compounds to identify those that may inhibit the main protease of SARS-CoV-2. We show that the shortlist of 84 candidates with the strongest predicted binding affinities is highly enriched (≥25%) in compounds experimentally validated in vivo or in vitro to have activity in SARS-CoV-2. The top candidates also include drugs and natural products not previously identified as having COVID-19 activity, thereby providing leads for experimental validation. This predictive in silico screening pipeline will be valuable for repurposing existing drugs and discovering new drug candidates against other medically important pathogens relevant to future pandemics.

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“…In keeping with this, the high safety of montelukast administration for the treatment of viral and respiratory diseases has been reported previously 2,7,11,12 . Mansour, S. et al 29 surveyed computational docking to assess the effects of montelukast on COVID-19 protease catalytic site. They showed a possible inhibitory portion of montelukast in binding to the Mpro catalytic site of the COVID-19 virus, which may modulate and inhibit the viral replication.…”

Section: Discussionmentioning

confidence: 99%

Treatment of SARS-CoV-2 (COVID-19) cases by the oral administration of montelukast tablets

Norouzi

2020

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According to the hypothesis, montelukast may have therapeutic action against severe acute respiratory syndrome (SARS) occurred by coronavirus 2 (CoV-19). The research was aimed to evaluate the therapeutic effects of montelukast tablet on coronavirus infectious disease (COVID-19) patients. A total of 20 COVID-19 confirmed patients were included in this study. The presence of COVID-19 infections in all patients was confirmed using real-time polymerase chain reaction (PCR) and computerized tomography (CT) scan. Confirmed cases were treated with oral administration of montelukast (10 mg) tablet for 10 days. The study population was included 18 to 82 years old patients (10 males and 10 females). The mean age of studied men and women individuals were 44.7±17 and 41±17.45 years, respectively. Frequency of respiratory distress, cough, abdominal cramps/diarrhea, fever, and odor disorder clinical signs amongst the examined patients were 85%, 90%, 20%, 70%, and 65%, respectively. Our findings revealed that all patients who were received 10 days of oral administration of montelukast tablets (10 mg) were recovered from the COVID-19 disease. Additionally, all of the clinical signs of COVID-19 patients, including respiratory distress, cough, and odor disorder, were gradually disappeared. Our findings revealed that widespread oral administration of montelukast tablets (10 mg) is a potential treatment for COVID-19 disease. However, several double-blind and multifactorial clinical trials should perform to determine the other clinical aspects of the treatment of COVID-19 patients by oral administration of montelukast.

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A Case for Montelukast in COVID-19: "The use of Computational Docking to estimate the effects of Montelukast on potential viral main protease catalytic site"

Cited by 5 publications

References 23 publications

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

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

Computational Repurposing of Drugs and Natural Products Against SARS-CoV-2 Main Protease (Mpro) as Potential COVID-19 Therapies

Treatment of SARS-CoV-2 (COVID-19) cases by the oral administration of montelukast tablets

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