Strategies Towards Protease Inhibitors for Emerging Flaviviruses
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Infections with flaviviruses are a continuing public health threat. In addition to vaccine development and vector control, the search for antiviral agents that alleviate symptoms in patients are of considerable interest. Among others, the flaviviral protease NS2B-NS3 is a promising drug target to inhibit viral replication. Flaviviral proteases share a high degree of structural similarity and substrate-recognition profile, which may facilitate a strategy towards development of pan-flaviviral...[Show more]
dc.contributor.author | Nitsche, Christoph | |
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dc.contributor.editor | Rolf Hilgenfeld | |
dc.contributor.editor | Subhash G. Vasudevan | |
dc.date.accessioned | 2019-04-23T01:05:04Z | |
dc.identifier.isbn | 978-981-10-8726-4 | |
dc.identifier.uri | http://hdl.handle.net/1885/160590 | |
dc.description.abstract | Infections with flaviviruses are a continuing public health threat. In addition to vaccine development and vector control, the search for antiviral agents that alleviate symptoms in patients are of considerable interest. Among others, the flaviviral protease NS2B-NS3 is a promising drug target to inhibit viral replication. Flaviviral proteases share a high degree of structural similarity and substrate-recognition profile, which may facilitate a strategy towards development of pan-flaviviral protease inhibitors. However, the success of various drug discovery attempts during the last decade has been limited by the nature of the viral enzyme as well as a lack of robust structural templates. Small-molecular, structurally diverse protease inhibitors have been reported to reach affinities in the lower micromolar range. Peptide-based, substrate-derived compounds are often nanomolar inhibitors, however, with highly compromised drug-likeness. With some exceptions, the antiviral cellular activity of most of the reported compounds have been patchy and insufficient for further development. Recent progress has been made in the elucidation of inhibitor binding using different structural methods. This will hopefully lead to more rational attempts for the identification of various lead compounds that may be successful in cellular assays, animal models and ultimately translated to patients. | |
dc.description.sponsorship | Funding by the Alexander von Humboldt Foundation is gratefully acknowledged. | |
dc.format.extent | 20 pages | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | Springer | |
dc.relation.ispartof | Dengue and Zika: Control and Antiviral Treatment Strategies | |
dc.relation.isversionof | 1st edition Edition | |
dc.rights | © Springer Nature Singapore Pte Ltd. 2018 | |
dc.subject | Protease | |
dc.subject | Inhibitor | |
dc.subject | Peptides | |
dc.subject | Small-molecular | |
dc.subject | Flavivirus | |
dc.subject | Dengue | |
dc.subject | West Nile | |
dc.subject | Zika | |
dc.title | Strategies Towards Protease Inhibitors for Emerging Flaviviruses | |
dc.type | Book chapter | |
local.description.notes | Imported from ARIES. The book is part of the Advances in experimental medicine and biology series volume 1062. | |
local.description.refereed | Yes | |
dc.date.issued | 2018 | |
local.identifier.absfor | 030401 - Biologically Active Molecules | |
local.identifier.ariespublication | u4485658xPUB2370 | |
local.publisher.url | https://www.springer.com/ | |
local.type.status | Accepted Version | |
local.contributor.affiliation | Nitsche, Christoph, College of Science, The Australian National University | |
local.bibliographicCitation.startpage | 175 | |
local.bibliographicCitation.lastpage | 186 | |
local.identifier.doi | 10.1007/978-981-10-8727-1_13 | |
local.identifier.absseo | 860803 - Human Pharmaceutical Treatments (e.g. Antibiotics) | |
dc.date.updated | 2019-03-12T07:34:12Z | |
local.bibliographicCitation.placeofpublication | Singapore | |
local.identifier.thomsonID | 000443965000014 | |
dcterms.accessRights | Open Access | |
dc.provenance | https://www.springer.com/gp/open-access/authors-rights/self-archiving-policy/2124 Authors whose work is accepted for publication in a non-open access Springer book may deposit their author’s accepted manuscript (AAM) in their institutional or funder repository, provided that the following conditions are observed. The author’s accepted manuscript is the version of the book manuscript accepted for publication after peer review, but prior to copyediting and typesetting for book series with a 12 months embargo (Publisher website as of 23/4/2019) | |
Collections | ANU Research Publications |
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