Development of lipid kinase inhibitors as novel broad-spectrum antivirals
Abstract/Contents
- Abstract
- Viral diseases are an unpredictable and growing threat to global health, as exemplified by recent outbreaks of Ebola virus, Zika virus, and of course the pandemic precipitated by SARS-CoV-2. These outbreaks highlight the fact that the modern medical arsenal, advanced as it is, has few options to fight viral infections. The current approach of developing a specific vaccine or antiviral for each virus also forces us to react to new threats as they arise, rather than having options ready to prevent a pandemic before it starts. To address this critical unmet need, I sought to develop and evaluate novel antiviral compounds with broad-spectrum activity against known viruses, as well as the potential to combat unexpected future threats. Our group's approach to developing novel antivirals was to target a host factor necessary for viral replication, rather than directly targeting the virus itself. This approach would present a higher barrier to resistance, as the drug target would not be under viral genetic control; if the host factor were critical to many viruses, this approach could also lead to broad-spectrum activity. We identified phosphatidylinositol-(4,5)-bisphosphate (PIP2) as host phospholipid necessary for the replication of hepatitis C virus, rhinovirus, and several enteroviruses, among other pathogens. I therefore worked to develop inhibitors of the kinases responsible for PIP2 biosynthesis, PI4K and PIP5K, and test their antiviral efficacy against these viruses. My work has resulted in novel highly-potent inhibitors of these lipid kinases, with excellent activity against a broad range of viruses. Several inhibitors have also shown unprecedented activity in animal models of enteroviruses. These inhibitors have the potential to progress to clinical use down the road and address a critical unmet medical need.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Basu, Kaustabh |
|---|---|
| Degree supervisor | Glenn, Jeffrey S, 1962- |
| Degree supervisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Glenn, Jeffrey S, 1962- |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Degree committee member | Bertozzi, Carolyn R, 1966- |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kaustabh Basu. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/tn799dw1824 |
Access conditions
- Copyright
- © 2022 by Kaustabh Basu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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