In Vitro and In Vivo Therapeutic Potential of 6,6′-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2
Abstract
:1. Introduction
2. Results
2.1. Determination of Half Maximal Inhibitory Concentration (IC50) of DTBN on Vero E6 Cells
2.2. DTBN Pretreatment of Vero E6 Cell Prior to Infection, Inhibits the Release of Infective Viral Particles to the Supernatant
2.3. DTBN Treatment of Vero E6 Cell following Infection, Inhibits the Release of Infective Viral Particles to the Supernatant
2.4. Survival of Infected Mice Treated with Vehicle or with DTBN
2.5. Expression of Viral Particles in Lungs of Vehicle and DTBN Treated Mice
2.6. In Silico Molecular Docking of DTBN and suramin to SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp)
2.7. Molecular Dynamic (MD) Simulation
3. Discussion
4. Materials and Methods
4.1. Cells
4.2. Virus
4.3. Cell Viability
4.4. Animal Experiments
4.5. Immunochemistry and Evaluation of Viral Presence in the Lung Sections
4.6. Computational Methodology
4.6.1. The Molecular Docking and MM-GBSA Refinement
ΔGBind Self cont + ΔGBind Solv GB + ΔGBind vdw)
4.6.2. Molecular Dynamics (MD) Simulation
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Motif | Range |
---|---|
Motif G | 499–511 |
Motif F | 544–560 |
Motif A | 612–626 |
Motif B | 678–710 |
Motif C | 753–767 |
Motif D | 771–796 |
Motif E | 810–820 |
S.No. | Compound | RdRp ΔG (Kcal/mol) | ACE2 ΔG (Kcal/mol) |
---|---|---|---|
1. | DTBN | −38.26 | −27.88 |
2. | Control | Suramin (−59.15) | MLN-4760 (−73.89) |
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Weiss, S.; Waidha, K.; Rajendran, S.; Benharroch, D.; Khalilia, J.; Levy, H.; Bar-David, E.; Golan-Goldhirsh, A.; Gopas, J.; Ben-Shmuel, A. In Vitro and In Vivo Therapeutic Potential of 6,6′-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2. Int. J. Mol. Sci. 2023, 24, 8327. https://doi.org/10.3390/ijms24098327
Weiss S, Waidha K, Rajendran S, Benharroch D, Khalilia J, Levy H, Bar-David E, Golan-Goldhirsh A, Gopas J, Ben-Shmuel A. In Vitro and In Vivo Therapeutic Potential of 6,6′-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2. International Journal of Molecular Sciences. 2023; 24(9):8327. https://doi.org/10.3390/ijms24098327
Chicago/Turabian StyleWeiss, Shay, Kamran Waidha, Saravanakumar Rajendran, Daniel Benharroch, Jannat Khalilia, Haim Levy, Elad Bar-David, Avi Golan-Goldhirsh, Jacob Gopas, and Amir Ben-Shmuel. 2023. "In Vitro and In Vivo Therapeutic Potential of 6,6′-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2" International Journal of Molecular Sciences 24, no. 9: 8327. https://doi.org/10.3390/ijms24098327