2022 journal article

Chalcones from Angelica keiskei (ashitaba) inhibit key Zika virus replication proteins

BIOORGANIC CHEMISTRY, 120.

By: M. Mottin *, L. Caesar *, D. Brodsky n, N. Mesquita*, K. Oliveira*, G. Noske  n, B. Sousa*, P. Ramos* ...

author keywords: Angelica keiskei; Ashitaba; Chalcones; Zika virus; Polymerase; Protease
MeSH headings : Angelica / chemistry; Animals; Chalcone / pharmacology; Chalcones / chemistry; Chalcones / pharmacology; Chlorocebus aethiops; Humans; RNA; RNA-Dependent RNA Polymerase; Vero Cells; Virus Replication; Zika Virus; Zika Virus Infection
TL;DR: With their simple structures and relative ease of modification, the chalcones represent attractive candidates for hit-to-lead optimization in the search of new anti-ZIKV therapeutics. (via Semantic Scholar)
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Source: Web Of Science
Added: July 18, 2022

Zika virus (ZIKV) is a dangerous human pathogen and no antiviral drugs have been approved to date. The chalcones are a group of small molecules that are found in a number of different plants, including Angelica keiskei Koidzumi, also known as ashitaba. To examine chalcone anti-ZIKV activity, three chalcones, 4-hydroxyderricin (4HD), xanthoangelol (XA), and xanthoangelol-E (XA-E), were purified from a methanol-ethyl acetate extract from A. keiskei. Molecular and ensemble docking predicted that these chalcones would establish multiple interactions with residues in the catalytic and allosteric sites of ZIKV NS2B-NS3 protease, and in the allosteric site of the NS5 RNA-dependent RNA-polymerase (RdRp). Machine learning models also predicted 4HD, XA and XA-E as potential anti-ZIKV inhibitors. Enzymatic and kinetic assays confirmed chalcone inhibition of the ZIKV NS2B-NS3 protease allosteric site with IC50s from 18 to 50 µM. Activity assays also revealed that XA, but not 4HD or XA-E, inhibited the allosteric site of the RdRp, with an IC50 of 6.9 µM. Finally, we tested these chalcones for their anti-viral activity in vitro with Vero cells. 4HD and XA-E displayed anti-ZIKV activity with EC50 values of 6.6 and 22.0 µM, respectively, while XA displayed relatively weak anti-ZIKV activity with whole cells. With their simple structures and relative ease of modification, the chalcones represent attractive candidates for hit-to-lead optimization in the search of new anti-ZIKV therapeutics.