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. 2025 Sep 8:e00907.
doi: 10.1002/cbdv.202500907. Online ahead of print.

Natural Inhibitors Against Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease From Three Vietnamese Bryophytes

Thi-Kim-Dung Le  1   2 , Gia-Hai Mach  3 , Nguyen-Khanh-Trinh Tram  4 , Nguyen-Kim-Tuyen Pham  5 , Ngoc-Khanh-Van Nguyen  6 , Thi-Minh-Dinh Tran  7 , Boi-Phong Vuong  3 , Ngoc-Hong Nguyen  8 , Thuc-Huy Duong  3 , Kiattawee Choowongkomon  9   10
Affiliations

Natural Inhibitors Against Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease From Three Vietnamese Bryophytes

Thi-Kim-Dung Le et al. Chem Biodivers. .

Abstract

Erythrodontium julaceum, Marchantia polymorpha, and Plagiochila bantamensis are widely distributed bryophytes in Vietnam. However, comprehensive chemical and biological data on their composition remain limited. Bio-guided isolation based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro inhibition was applied to these species, resulting in the identification of 23 metabolites. Compound P8 is a new natural compound. Subsequently, the SARS-CoV-2 Mpro inhibition of the isolated compounds revealed that bisbibenzyl- and 3-benzylphthalide-type compounds exhibit bioactivity. Among the tested compounds, isoriccardin C (M2) and julacelide (E1) exhibited significant activity, with IC50 values of 15.7 and 2.84 µg/mL, respectively. Molecular docking results further supported their strong activity.

Keywords: 3‐benzylphthalide; Erythrodontium julaceum; Marchantia polymorpha; Plagiochila bantamensis; SARS‐CoV‐2 Mpro inhibition; bisbibenzyl.

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