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

Publication date: Jul 19, 2024

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 IC 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 IC 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 IC values of 76. 0, 31. 9, and 14. 9 μM, respectively.

Concepts Keywords
Acetylacuminolide 229e
Alphacoronavirus Annonaceae
Bark Antiviral
Molecular Bark
Rare Foetida
Hcov
Isolation
Labdane
Lc
Molecular
Ms
Neo
Networking
Uvaria
Values

Semantics

Type Source Name
disease IDO assay
disease VO Viruses

Original Article

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