Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in "Super-Open" Conformation
Issued Date
2023-04-30
Resource Type
eISSN
19994915
Scopus ID
2-s2.0-85160380879
Pubmed ID
37243192
Journal Title
Viruses
Volume
15
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Viruses Vol.15 No.5 (2023)
Suggested Citation
Meewan I., Shiryaev S.A., Kattoula J., Huang C.T., Lin V., Chuang C.H., Terskikh A.V., Abagyan R. Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in "Super-Open" Conformation. Viruses Vol.15 No.5 (2023). doi:10.3390/v15051106 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82965
Title
Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in "Super-Open" Conformation
Other Contributor(s)
Abstract
The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barré syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the "super-open" conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections.