Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure
Abstract
:1. Introduction
2. Results
2.1. MLN and Exocytosis
2.2. MLN and Endocytosis
2.2.1. Molecular Docking and MLN-CTD Interactions
2.2.2. Molecular Dynamics and MM-PBSA Calculations
2.3. Reverse Target Searches for Identification of SARS-CoV-2 Proteome Binding Pockets
2.4. SARS-CoV-2 Inhibition by MLN and Test Compounds Using SIH Assay Immunohistochemistry
2.5. Viral Entry and Spread Assays
2.6. MLN Cytotoxicity Evaluation
3. Discussion
4. Materials and Methods
4.1. MLN and Exocytosis
4.2. MLN and Endocytosis
4.2.1. Protein Structure Retrieval and Preprocessing
4.2.2. Molecular Docking of MLN to CTD
4.2.3. Molecular Dynamics Simulations of MLN-CTD Complexes
4.3. Reverse Target Searches for Novel Binding Pocket
4.4. Experimental Studies
4.4.1. SARS-CoV-2 Strains and Cell Lines
4.4.2. Antiviral Inhibition Assays
Evaluation of Viral Inhibition by MLN Using Spike Immunohistochemistry Assay
Evaluation of Viral Inhibition by MLN Using Plaque Assay
MLN and Virus Entry and Spread Inhibition Assay
4.4.3. Cytotoxicity Assays
5. Patents
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Asiedu, S.O.; Gupta, Y.; Nicolaescu, V.; Gula, H.; Caulfield, T.R.; Durvasula, R.; Kempaiah, P.; Kwofie, S.K.; Wilson, M.D. Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure. Int. J. Mol. Sci. 2023, 24, 7151. https://doi.org/10.3390/ijms24087151
Asiedu SO, Gupta Y, Nicolaescu V, Gula H, Caulfield TR, Durvasula R, Kempaiah P, Kwofie SK, Wilson MD. Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure. International Journal of Molecular Sciences. 2023; 24(8):7151. https://doi.org/10.3390/ijms24087151
Chicago/Turabian StyleAsiedu, Seth Osei, Yash Gupta, Vlad Nicolaescu, Haley Gula, Thomas R. Caulfield, Ravi Durvasula, Prakasha Kempaiah, Samuel K. Kwofie, and Michael D. Wilson. 2023. "Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure" International Journal of Molecular Sciences 24, no. 8: 7151. https://doi.org/10.3390/ijms24087151