In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells and Viruses
2.2. Compounds and Cytopathic Effect (CPE) Reduction Assay
2.3. Field-Based Pharmacophore Modeling
2.4. Immunoassays
2.5. Plaque Assay
2.6. Confocal Microscopy
2.7. Polykaryon Assay
2.8. Trypsin Protection Assay
2.9. In Vivo Study
2.10. Statistical Analysis
3. Results
3.1. Anti-Influenza Viral Activity of Nylidrin and Its Analogues
3.2. Field-Based Pharmacophore Analysis of Phenyl Aminoethanol Compounds
3.3. Abnormal Accumulation of Nucleoprotein (NP) in the Cytoplasm by Nylidrin
3.4. Inhibition of HA2 Fusion Activity by Nylidrin
3.5. In Vivo Antiviral Efficacy of Nylidrin
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | CC50 (μM) a to MDCK Cells | EC50 (μM) b against Influenza Viruses (S.I. c) | Function | ||
---|---|---|---|---|---|
A/ Puerto Rico/8/1934 (H1N1) | A/Hong Kong/8/1968 (H3N2) | B/Lee/40 | |||
Nylidrin | 549.2 ± 0.5 | 7.2 ± 0.2 | 12.1 ± 1.6 | >100.0 | β2-Adrenergic receptor agonist |
(76.3) | (45.4) | (N.D.) | |||
Ifenprodil | 488.2 ± 0.5 | 6.6 ± 0.4 | 16.9 ± 3.0 | >100.0 | N-methyl-D-aspartate receptor 2B antagonist |
(74.0) | (29.0) | (N.D. d) | |||
Labetalol | 498.1 ± 0.5 | >100.0 | 44.0 ± 9.7 | >100.0 | α1- and β1/β2-Adrenergic receptor antagonist |
(N.D.) | (>11.3) | (N.D.) | |||
Ritodrine | >900.0 | >100.0 | >100.0 | >100.0 | β2-Adrenergic receptor agonist |
(N.D.) | (N.D.) | (N.D.) | |||
Fenoterol | >900.0 | >100.0 | >100.0 | >100.0 | β2-Adrenergic receptor agonist |
(N.D.) | (N.D.) | (N.D.) | |||
Eliprodil | >900.0 | >100.0 | 58.1 ± 6.4 | >100.0 | N-methyl-D-aspartate antagonist |
(N.D.) | (>15.5) | (N.D.) | |||
Clenbuterol | >900.0 | 9.4 ± 4.6 | >100.0 | >100.0 | β2-Adrenergic receptor agonist |
(>96.3) | (N.D.) | (N.D.) | |||
Bambuterol | >900.0 | >100.0 | >100.0 | >100.0 | β2-Adrenergic receptor agonist |
(N.D.) | (N.D.) | (N.D.) | |||
AMTe | >900.0 | >100.0 | 0.8 ± 0.1 | >100.0 | - f |
(N.D.) | (>1200) | (N.D.) | |||
RBV g | >900.0 | 18.4 ± 3.4 | 15.7 ± 2.7 | 13.8 ± 0.2 | - |
(>48.9) | (>57.5) | (>65.5) | |||
OSV-C h | >900.0 | 0.04 ± 0.01 | <0.005 | 0.8 ± 0.03 | - |
(>25,714) | (>180,000) | (>1125) |
Compound | CC50 (μM) a to MDCK Cells | EC50 (μM) b against Influenza Viruses (S.I. c) | ||||||
---|---|---|---|---|---|---|---|---|
A/California /7/2009 (H1N1) | A/Brisbane /59/2007 (H1N1) | A/Seoul /11/1988 (H3N2) | A/Perth /16/2009 (H3N2) | A/Brisbane /10/2007 (H3N2) | A/Victoria /361/2011-like (H3N2) | B/Brisbane /60/2008 | ||
Nylidrin | 549.2 ± 0.5 | 1.7 ± 0.5 | 3.5 ± 1.6 | 38.8 ± 19.4 | >100.0 | >100.0 | >100.0 | >100.0 |
(332.8) | (156.9) | (14.3) | (N.D. d) | (N.D.) | (N.D.) | (N.D.) | ||
Ifenprodil | 488.2 ± 0.5 | 1.1 ± 0.1 | 5.1 ± 0.3 | 37.9 ± 7.7 | >100.0 | >100.0 | >100.0 | >100.0 |
(465.0) | (96.7) | (14.5) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | ||
Labetalol | 498.1 ± 0.5 | >100.0 | >100.0 | >100.0 | >100.0 | >100.0 | >100.0 | >100.0 |
(N.D.) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | ||
Eliprodil | >900.0 | >100.0 | 53.1 ± 0.3 | >100.0 | >100.0 | >100.0 | >100.0 | >100.0 |
(N.D.) | (>16.9) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | ||
Clenbuterol | >900.0 | 13.7 ± 3.6 | 12.9 ± 0.3 | >100.0 | >100.0 | >100.0 | >100.0 | >100.0 |
(>65.9) | (>69.8) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | ||
AMT e | >900.0 | >100.0 | 1.2 ± 0.4 | 0.3 ± 0.1 | >100.0 | >100.0 | >100.0 | >100.0 |
(N.D.) | (>750) | (>1831) | (N.D.) | (N.D.) | (N.D.) | (N.D.) | ||
RBV f | >900.0 | 52.5 ± 1.5 | 24.1 ± 0.5 | 10.5 ± 4.2 | 33.8 ± 11.6 | 12.6 ± 6.4 | 33.4 ± 8.8 | 25.6 ± 0.3 |
(>17.2) | (>37.3) | (>52.3) | (>26.6) | (>71.4) | (>16.4) | (>35.2) | ||
OSV-C g | >900.0 | 0.02 ± 0.0 | 0.02 ± 0.0 | <0.005 | 0.03 ± 0.02 | 0.53 ± 0.16 | <0.005 | 53.1 ± 25.25 |
(>58,065) | (>58,065) | (>180,000) | (>30,000) | (>1714) | (>180,000) | (>17.0) |
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Jang, Y.; Shin, J.S.; Lee, J.-Y.; Shin, H.; Kim, S.J.; Kim, M. In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus. Viruses 2020, 12, 581. https://doi.org/10.3390/v12050581
Jang Y, Shin JS, Lee J-Y, Shin H, Kim SJ, Kim M. In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus. Viruses. 2020; 12(5):581. https://doi.org/10.3390/v12050581
Chicago/Turabian StyleJang, Yejin, Jin Soo Shin, Joo-Youn Lee, Heegwon Shin, Sang Jick Kim, and Meehyein Kim. 2020. "In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus" Viruses 12, no. 5: 581. https://doi.org/10.3390/v12050581