Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Transcription Initiation of Vesiculoviruses
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Viruses
2.3. VSV Cell Killing Assay in a 384-Well Format
2.4. VSV Cell Killing Assay in a 96-Well Format
2.5. Other VSV Cell Infection Assays
2.6. Preparation of Viral RNPs and Proteins
2.7. In Vitro Transcription and Capping Assays
2.8. In Vitro Pulse-Chase Lerna Synthesis Assay
3. Results
3.1. Discovery of Vesiculopolins as VSV RdRp Inhibitors
3.2. Antiviral Activities of Vesiculopolins A and B against Rhabdoviruses
3.3. The Mode of Action of Vesiculopolin A in Inhibition of VSV RdRp
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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% Inhibition | |||||
---|---|---|---|---|---|
ChemBridge ID # | VPI | Metabolic Shut-down 1 (CCK Assay) | Nuclear Condensation 1 (Cell Imaging) | mRNA Synthesis 2 (In vitro Transcription) | |
1 | 53425003 | A | 105 | 98 | 99 |
2 | 20208871 | B | 102 | 92 | 89 |
3 | 66896553 | C | 58 | 63 | 72 |
4 | 35540582 | D | 55 | 57 | 72 |
5 | 80285323 | E | 50 | 94 | 72 |
6 | 10443614 | F | 48 | 69 | 34 |
7 | 37324373 | G | 46 | 54 | 68 |
8 | 52194062 | 44 | 51 | 10 | |
9 | 69805228 | 39 | 0 | n.d. | |
10 | 43534388 | 35 | 10 | n.d. | |
11 | 90353655 | H | 34 | 53 | 73 |
12 | 81699442 | 31 | 0 | n.d. | |
13 | 66349773 | 30 | 9 | n.d. |
Compound | BHK-21 Cells | HeLa Cells | ||||||
---|---|---|---|---|---|---|---|---|
Cytotoxicity | Anti-VSV Activity | Anti-CHPV Activity | Cytotoxicity | Anti-VSV Activity | ||||
CC50 1 | IC50 1 | SI 2 | IC50 1 | SI 2 | CC50 1 | IC50 1 | SI 2 | |
VPI A | >100 | 2.0 ± 0.1 | >50 | 7.9 ± 0.4 | >13 | >100 | 0.42 ± 0.02 | >240 |
VPI B | >100 | 6.2 ± 0.2 | >16 | 11 ± 1 | >9 | >100 | 1.1 ± 0.1 | >91 |
Ribavirin | 86 ± 0.5 | >100 | <1 | >100 | <1 | >100 | 15 ± 1 | >7 |
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Ogino, M.; Fedorov, Y.; Adams, D.J.; Okada, K.; Ito, N.; Sugiyama, M.; Ogino, T. Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Transcription Initiation of Vesiculoviruses. Viruses 2019, 11, 856. https://doi.org/10.3390/v11090856
Ogino M, Fedorov Y, Adams DJ, Okada K, Ito N, Sugiyama M, Ogino T. Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Transcription Initiation of Vesiculoviruses. Viruses. 2019; 11(9):856. https://doi.org/10.3390/v11090856
Chicago/Turabian StyleOgino, Minako, Yuriy Fedorov, Drew J. Adams, Kazuma Okada, Naoto Ito, Makoto Sugiyama, and Tomoaki Ogino. 2019. "Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Transcription Initiation of Vesiculoviruses" Viruses 11, no. 9: 856. https://doi.org/10.3390/v11090856
APA StyleOgino, M., Fedorov, Y., Adams, D. J., Okada, K., Ito, N., Sugiyama, M., & Ogino, T. (2019). Vesiculopolins, a New Class of Anti-Vesiculoviral Compounds, Inhibit Transcription Initiation of Vesiculoviruses. Viruses, 11(9), 856. https://doi.org/10.3390/v11090856