Discovery of Inhibitors Targeting the RNA-Dependent RNA Polymerase of the Zika Virus

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• Zika virus (ZIKV), an *Orthoflavivirus*, is associated with severe neurological and developmental conditions.
• There are currently no approved treatments or vaccines for ZIKV infections, posing a significant global health challenge.

Purpose of the Study:

• To identify novel inhibitors of ZIKV's RNA-dependent RNA polymerase (RdRp), an enzyme crucial for viral replication.
• To adapt and optimize the malachite green colorimetric assay for screening ZIKV RdRp activity.

Main Methods:

• Screening of 204 compounds from the National Cancer Institute's Natural Product Set IV.
• Utilizing an optimized malachite green colorimetric assay to measure ZIKV RdRp activity.
• Identifying compounds that demonstrate inhibitory effects on the target enzyme.

Main Results:

• Two natural compounds, purpurogallin and digallic acid, were identified as inhibitors of ZIKV RdRp.
• The malachite green assay was successfully optimized for ZIKV RdRp activity screening.
• The identified compounds represent potential leads for antiviral drug development.

Conclusions:

• Purpurogallin and digallic acid show promise as inhibitors of ZIKV replication.
• Further research is warranted to determine the precise mechanisms of action and therapeutic potential of these compounds.
• This study provides a foundation for developing new ZIKV therapeutics.