Genetics and biochemistry of Dengue virus inhibitors
Abstract/Contents
- Abstract
- Drug resistance remains a major obstacle in developing therapeutic treatments for viruses and other diseases. Typical solutions proposed for this problem are the development of host-targeted antivirals and multiple-drug therapy. Work presented in this thesis builds on the new paradigm of dominant drug targets, which prevent the outgrowth of drug resistant variants by virtue of their genetic properties. Ideally, for any emerging or neglected viral disease we would be able to utilize all three strategies mentioned through direct-acting and host-targeted antiviral compounds with good drug resistance profiles. Here, I describe one direct-acting antiviral compound in detail, a viral protease inhibitor. I show that specific dengue NS2B/3 protease precursors, which accumulate upon treatment with the protease inhibitor, have dominant effects on wild-type dengue virus. We were unable to isolate adaptive mutations to this compound, suggesting that selection is blunted as predicted for dominant drug targets. I then show that there are multiple FDA-approved compounds with a high degree of chemical similarity, and importantly, similar biologic activities, to antiviral tool compounds commonly used in the laboratory. Several of these are highly promising as potential dengue or Zika therapies. Through this work, I hope to show that practical treatments for widespread diseases such as dengue and Zika viruses are within our grasp.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Constant, David Angus |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Kirkegaard, Karla |
| Thesis advisor | Kirkegaard, Karla |
| Thesis advisor | Carette, Jan, 1971- |
| Thesis advisor | Mudgett, Mary Beth, 1967- |
| Thesis advisor | Stearns, Tim |
| Advisor | Carette, Jan, 1971- |
| Advisor | Mudgett, Mary Beth, 1967- |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | David Angus Constant. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by David Angus Constant
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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