Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of Neo-uvaria foetida (Annonaceae) using LC-MS/MS-Based Molecular Networking

• Published in: Journal of Natural Products
• Main Author: Sukumaran S.Y.; Herrscher C.; Rasol N.E.; Othman M.A.; Liew S.Y.; Ismail N.H.; Séron K.; Litaudon M.; Awang K.; El Kalamouni C.; Apel C.; Zahari A.
• Format: Article
• Language: English
• Published: American Chemical Society 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85199047842&doi=10.1021%2facs.jnatprod.4c00342&partnerID=40&md5=14a6ee6a0c48a75d29870fa05c7e54fa

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 μg/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 μM, 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 μM, respectively. © 2024 American Chemical Society and American Society of Pharmacognosy