Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of Neo-uvaria foetida (Annonaceae) using LC-MS/MS-Based Molecular Networking
Document Type
Article
Publication Date
7-1-2024
Abstract
In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC50 values of 3.8 and 7.8 mu g/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8-epi-acuminolide (1) and foetidalabdane A (4), and three known labdane diterpenoids, acuminolide (2), 17-O-acetylacuminolide (3), and spiroacuminolide (5). A new norlabdane diterpene, 16-foetinorlabdoic acid (6), was also isolated and identified. Excluding compounds 5 and 6, all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC50 values of 63.3 and 93.5 mu M, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1, 2, and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC50 values of 76.0, 31.9, and 14.9 mu M, respectively.
Divisions
CHEMISTRY
Funders
Ministry of Education, Malaysia (FRGS/1/2021/STG04/UM/02/12),Conseil Regional de La Reunion (20201437-0027601),France 2030 program,ANRS I MIE (ANRS-23-PEPR-MIE004),OHSEA project under the Institute de Recherche Pour Le Development, France (IF029-2022),Universite Paris-Saclay,Agence Nationale de la Recherche (ANR) (ANR-11-IDEX-0003-02 (10-LABX-0033))
Publication Title
Journal of Natural Products
Volume
87
Issue
8
Publisher
American Chemical Society
Publisher Location
1155 16TH ST, NW, WASHINGTON, DC 20036 USA