key: cord-0755146-yiifbazj
authors: Li, Xia; Gao, Jie; Li, Miaomiao; Cui, Hao; Jiang, Wei; Tu, Zong-cai; Yuan, Tao
title: Aromatic Cadinane Sesquiterpenoids from the Fruiting Bodies of Phellinus pini Block SARS-CoV-2 Spike–ACE2 Interaction
date: 2021-08-05
journal: J Nat Prod
DOI: 10.1021/acs.jnatprod.1c00426
sha: 7efd2cbbdf747b070d555cf6d9a1f7294f8378e4
doc_id: 755146
cord_uid: yiifbazj

[Image: see text] 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 Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A–D (1–4), 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(50) values ranging from 64.5 to 99.1 μM. A molecular docking study showed the disruption of the interaction of compound 1 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.

. 1 

The conformers for compounds 2 and 3 were generated by the MM2 force field in ChemBio3D Ultra 16.0 software overlaid with the key correlations observed in the NOESY experiment. 1 The conformers were then reoptimized using DFT at the M062X/def2svp level in vacuum in the Gaussian 16 program. 2 The M062X/def2svp harmonic vibrational frequencies were further calculated to confirm their stability. 

A series of β-carboline alkaloids from the seeds of Peganum harmala show G-quadruplex interactions