Abstract
Aim: The identification of drugs for the coronavirus disease-19 pandemic remains urgent. In this manner, drug repurposing is a suitable strategy, saving resources and time normally spent during regular drug discovery frameworks. Essential for viral replication, the main protease has been explored as a promising target for the drug discovery process. Materials & methods: Our virtual screening pipeline relies on the known 3D properties of noncovalent ligands and features of crystalized complexes, applying consensus analyses in each step. Results: Two oral (bedaquiline and glibenclamide) and one buccal drug (miconazole) presented 3D similarity to known ligands, reasonable predicted binding modes and micromolar predicted binding affinity values. Conclusion: We identified three approved drugs as promising inhibitors of the main viral protease and suggested design insights for future studies for development of novel selective inhibitors.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antiviral Agents / chemistry
-
Antiviral Agents / pharmacology*
-
Betacoronavirus / drug effects
-
Betacoronavirus / enzymology*
-
COVID-19
-
Coronavirus 3C Proteases
-
Coronavirus Infections / drug therapy*
-
Coronavirus Infections / virology
-
Cysteine Endopeptidases / metabolism
-
Diarylquinolines / chemistry
-
Diarylquinolines / pharmacology
-
Drug Design
-
Drug Discovery*
-
Glyburide / chemistry
-
Glyburide / pharmacology
-
Humans
-
Ligands
-
Miconazole / chemistry
-
Miconazole / pharmacology
-
Models, Molecular
-
Molecular Docking Simulation
-
Pandemics
-
Pneumonia, Viral / drug therapy*
-
Pneumonia, Viral / virology
-
Protease Inhibitors / chemistry
-
Protease Inhibitors / pharmacology*
-
SARS-CoV-2
-
Viral Nonstructural Proteins / antagonists & inhibitors*
-
Viral Nonstructural Proteins / metabolism
Substances
-
Antiviral Agents
-
Diarylquinolines
-
Ligands
-
Protease Inhibitors
-
Viral Nonstructural Proteins
-
bedaquiline
-
Miconazole
-
Cysteine Endopeptidases
-
Coronavirus 3C Proteases
-
Glyburide