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

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) M pro 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 M pro 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 IC 50 values of 15.7 and 2.84 µg/mL, respectively. Molecular docking results further supported their strong activity.