Aromatic Cadinane Sesquiterpenoids from the Fruiting Bodies of <i>Phellinus pini</i> Block SARS-CoV-2 Spike-ACE2 Interaction.
Li X, Gao J, Li M, Cui H, Jiang W, Tu ZC, Yuan T.
The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of <i>Phellinus pini</i> led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (<b>1</b>-<b>4</b>), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic cadinane sesquiterpenoids inhibited the SARS-CoV-2 spike-ACE2 interaction, with IC<sub>50</sub> values ranging from 64.5 to 99.1 μM. A molecular docking study showed the disruption of the interaction of compound <b>1</b> via hydrogen interactions with Arg403, Asp405, and Arg408 of SARS-CoV-2 RBD and Arg393 and His34 residues of ACE2. These results suggested that aromatic cadinane sesquiterpenoids might be useful in developing agents for COVID-19.