AI Article Synopsis
- - Zika virus (ZIKV) infections are linked to serious health issues like microcephaly in newborns and Guillain-Barre syndrome in adults, with no current vaccines or antiviral treatments available.
- - The NS3 protease and its co-factor NS2B play a crucial role in processing viral proteins, making them a key target for drug development.
- - A successful crystallographic study identified 48 compounds that bind to the NS2B-NS3 protease, along with 6 additional fragments targeting a possible allosteric site, paving the way for new inhibitors to be developed.
Article Abstract
Zika virus (ZIKV) infections cause microcephaly in new-borns and Guillain-Barre syndrome in adults raising a significant global public health concern, yet no vaccines or antiviral drugs have been developed to prevent or treat ZIKV infections. The viral protease NS3 and its co-factor NS2B are essential for the cleavage of the Zika polyprotein precursor into individual structural and non-structural proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 48 binders with diverse chemical scaffolds were identified in the active site of the protease, with another 6 fragment hits observed in a potential allosteric binding site. Our work provides potential starting points for the development of potent NS2B-NS3 protease inhibitors. Furthermore, we have structurally characterized a potential allosteric binding pocket, identifying opportunities for allosteric inhibitor development.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092485 | PMC |
| http://dx.doi.org/10.1101/2024.04.29.591502 | DOI Listing |
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