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Published on: July 15, 2019
Anti-HCV and anti-malaria agent, potential candidates to repurpose for coronavirus infection: Virtual screening,
Faezeh Sadat Hosseini1, Massoud Amanlou2
1Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Insights
Computational screening identified simeprevir and pyronaridine as potential treatments for coronavirus disease 2019 (COVID-19). These drugs show promise for repurposing against SARS-CoV-2 main protease, offering new therapeutic avenues.
Area of Science:
- Computational drug discovery
- Virology
- Medicinal chemistry
Background:
- Coronavirus disease 2019 (COVID-19) rapidly spread globally, causing a pandemic.
- Effective treatments for COVID-19 remain limited, necessitating novel therapeutic strategies.
- The main protease of SARS-CoV-2 is a critical target for antiviral drug development.
Purpose of the Study:
- To identify potential small molecule inhibitors targeting the SARS-CoV-2 main protease.
- To explore drug repurposing opportunities for existing approved medications.
- To utilize computational methods for efficient drug candidate screening.
Main Methods:
- Virtual screening of two drug databases (FDA-approved and world-approved) against the SARS-CoV-2 main protease structure.
- Docking simulations to assess ligand binding affinity and interactions.
- Molecular dynamics simulations (150 ns) to evaluate the stability and behavior of top-ranked compounds.
- Binding energy calculations using the MMPBSA approach for further validation.
Main Results:
- Simeprevir (an HCV protease inhibitor) and pyronaridine (an antimalarial agent) demonstrated favorable binding to the SARS-CoV-2 main protease.
- These candidates possess beneficial properties, including broad-spectrum antiviral potential and suitable ADME profiles.
- The computational analysis suggests these drugs are promising candidates for COVID-19 treatment repurposing.
Conclusions:
- Simeprevir and pyronaridine were identified as potential drug candidates for COVID-19 treatment.
- The combined virtual screening and molecular dynamics simulation approach proved effective in selecting these candidates.
- Further investigation into simeprevir and pyronaridine could lead to new therapeutic options for COVID-19.
Aims:
Coronavirus disease 2019 (COVID-19) has appeared in Wuhan, China but the fast transmission has led to its widespread prevalence in various countries, which has made it a global concern. Another concern is the lack of definitive treatment for this disease. The researchers tried different treatment options which are not specific. The current study aims to identify potential small molecule inhibitors against the main protease protein of SARS-CoV-2 by the computational approach.
Main Methods:
In this study, a virtual screening procedure employing docking of the two different datasets from the ZINC database, including 1615 FDA approved drugs and 4266 world approved drugs were used to identify new potential small molecule inhibitors for the newly released crystal structure of main protease protein of SARS-CoV-2. In the following to validate the docking result, molecular dynamics simulations were applied on selected ligands to identify the behavior and stability of them in the binding pocket of the main protease in 150 nanoseconds (ns). Furthermore, binding energy using the MMPBSA approach was also calculated.
Key Findings:
The result indicates that simeprevir (Hepatitis C virus NS3/4A protease inhibitor) and pyronaridine (antimalarial agent) could fit well to the binding pocket of the main protease and because of some other beneficial features including broad-spectrum antiviral properties and ADME profile, they might be a promising drug candidate for repurposing to the treatment of COVID-19.
Significance:
Simeprevir and pyronaridine were selected by the combination of virtual screening and molecular dynamics simulation approaches as a potential candidate for treatment of COVID-19.
