Substrate profiling of Zika virus NS2B-NS3 protease
- PMID: 27714789
- DOI: 10.1002/1873-3468.12443
Substrate profiling of Zika virus NS2B-NS3 protease
Abstract
Zika virus (ZIKV), isolated from macaques in Uganda in 1947, was not considered to be a dangerous human pathogen. However, this view has recently changed as ZIKV infections are now associated with serious pathological disorders including microcephaly and Guillain-Barré syndrome. Similar to other viruses in the Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible for viral protein processing and replication. Herein, we report the expression of an active NS3pro domain fused with the NS2B cofactor (NS2BLN NS3pro ) in a prokaryotic expression system and profile its specificity for synthesized FRET-type substrate libraries. Our findings pave way for screening potential intracellular substrates of NS3 and for developing specific inhibitors of this ZIKV protease.
Keywords: NS2B-NS3 protease; Zika virus; combinatorial chemistry; substrate library; substrate mapping.
© 2016 Federation of European Biochemical Societies.
Similar articles
-
Extended substrate specificity and first potent irreversible inhibitor/activity-based probe design for Zika virus NS2B-NS3 protease.Antiviral Res. 2017 Mar;139:88-94. doi: 10.1016/j.antiviral.2016.12.018. Epub 2016 Dec 26. Antiviral Res. 2017. PMID: 28034744
-
Profiling of flaviviral NS2B-NS3 protease specificity provides a structural basis for the development of selective chemical tools that differentiate Dengue from Zika and West Nile viruses.Antiviral Res. 2020 Mar;175:104731. doi: 10.1016/j.antiviral.2020.104731. Epub 2020 Jan 31. Antiviral Res. 2020. PMID: 32014497
-
The Structure of the Zika Virus Protease, NS2B/NS3pro.Adv Exp Med Biol. 2018;1062:131-145. doi: 10.1007/978-981-10-8727-1_10. Adv Exp Med Biol. 2018. PMID: 29845530 Review.
-
Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.Antiviral Res. 2017 Jul;143:218-229. doi: 10.1016/j.antiviral.2017.04.015. Epub 2017 Apr 29. Antiviral Res. 2017. PMID: 28461069 Free PMC article.
-
The Inhibition of NS2B/NS3 Protease: A New Therapeutic Opportunity to Treat Dengue and Zika Virus Infection.Int J Mol Sci. 2024 Apr 16;25(8):4376. doi: 10.3390/ijms25084376. Int J Mol Sci. 2024. PMID: 38673962 Free PMC article. Review.
Cited by
-
C-Terminal Extended Hexapeptides as Potent Inhibitors of the NS2B-NS3 Protease of the ZIKA Virus.Front Med (Lausanne). 2022 Jul 6;9:921060. doi: 10.3389/fmed.2022.921060. eCollection 2022. Front Med (Lausanne). 2022. PMID: 35872792 Free PMC article.
-
Zika Virus NS3 Protease Pharmacophore Anchor Model and Drug Discovery.Sci Rep. 2020 Jun 2;10(1):8929. doi: 10.1038/s41598-020-65489-w. Sci Rep. 2020. PMID: 32488021 Free PMC article.
-
Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?Front Microbiol. 2017 Aug 22;8:1554. doi: 10.3389/fmicb.2017.01554. eCollection 2017. Front Microbiol. 2017. PMID: 28878742 Free PMC article. Review.
-
Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor.Front Pharmacol. 2020 Oct 21;11:514313. doi: 10.3389/fphar.2020.514313. eCollection 2020. Front Pharmacol. 2020. PMID: 33192499 Free PMC article.
-
One Step Beyond: Design of Substrates Spanning Primed Positions of Zika Virus NS2B-NS3 Protease.ACS Med Chem Lett. 2018 Aug 28;9(10):1025-1029. doi: 10.1021/acsmedchemlett.8b00316. eCollection 2018 Oct 11. ACS Med Chem Lett. 2018. PMID: 30344911 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
