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Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as M Pro inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
- Source :
-
BMC research notes [BMC Res Notes] 2020 Nov 11; Vol. 13 (1), pp. 527. Date of Electronic Publication: 2020 Nov 11. - Publication Year :
- 2020
-
Abstract
- Objectives: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions.<br />Results: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong M <superscript>Pro</superscript> inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent M <superscript>Pro</superscript> inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant M <superscript>Pro</superscript> inhibition.
- Subjects :
- Amides chemistry
Amides pharmacology
Antiviral Agents chemistry
Benzaldehydes chemistry
Chloroquine chemistry
Computer Simulation
Coronavirus 3C Proteases
Cysteine Endopeptidases
Cysteine Proteinase Inhibitors chemistry
Humans
Hydroxychloroquine chemistry
Hydroxychloroquine pharmacology
Laurates chemistry
Laurates pharmacology
Microbial Sensitivity Tests
Models, Molecular
Monoglycerides chemistry
Monoglycerides pharmacology
Pyrazines chemistry
Pyrazines pharmacology
SARS-CoV-2
Structure-Activity Relationship
Tetrodotoxin chemistry
Tetrodotoxin pharmacology
Antiviral Agents pharmacology
Betacoronavirus drug effects
Chloroquine pharmacology
Cysteine Proteinase Inhibitors pharmacology
Viral Nonstructural Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1756-0500
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC research notes
- Publication Type :
- Academic Journal
- Accession number :
- 33176880
- Full Text :
- https://doi.org/10.1186/s13104-020-05379-6