dc.contributor.author
Voss, Saan
dc.contributor.author
Rademann, Jörg
dc.contributor.author
Nitsche, Christoph
dc.date.accessioned
2024-07-04T06:53:21Z
dc.date.available
2024-07-04T06:53:21Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/44116
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-43826
dc.description.abstract
Flaviviruses can cause severe illness in humans. Effective and safe vaccines are available for some species; however, for many flaviviruses disease prevention or specific treatments remain unavailable. The viral replication cycle depends on the proteolytic activity of the NS2B-NS3 protease, which releases functional viral proteins from a non-functional polyprotein precursor, rendering the protease a promising drug target. In this study, we characterised recombinant NS2B-NS3 proteases from ten flaviviruses including three unreported proteases from the Usutu, Kyasanur forest disease and Powassan viruses. All protease constructs comprise a covalent Gly4-Ser-Gly4 linker connecting the NS3 serine protease domain with its cofactor NS2B. We conducted a comprehensive cleavage site analysis revealing areas of high conversion. While all proteases were active in enzymatic assays, we noted a 1000-fold difference in catalytic efficiency across proteases from different flaviviruses. Two bicyclic peptide inhibitors displayed anti-pan-flaviviral protease activity with inhibition constants ranging from 10 to 1000 nM.
en
dc.format.extent
5 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Protease inhibitors
en
dc.subject
Broad-spectrum
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Characterisation of ten NS2B-NS3 proteases: Paving the way for pan-flavivirus drugs
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
105878
dcterms.bibliographicCitation.doi
10.1016/j.antiviral.2024.105878
dcterms.bibliographicCitation.journaltitle
Antiviral Research
dcterms.bibliographicCitation.volume
226
dcterms.bibliographicCitation.url
https://doi.org/10.1016/j.antiviral.2024.105878
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
![This authority value has been confirmed as accurate by an interactive user](/cache_202e45ad85b55efaeb29160f63cd3f3b/themes/FuCD/images/authority_control/invisible.gif)
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1872-9096
refubium.resourceType.provider
WoS-Alert