Axial Chiral Binaphthoquinone and Perylenequinones from the Stromata of <i>Hypocrella bambusae</i> Are SARS-CoV-2 Entry Inhibitors.
Li YT, Yang C, Wu Y, Lv JJ, Feng X, Tian X, Zhou Z, Pan X, Liu S, Tian LW.
A new axial chiral binaphtoquinone, hypocrellone (<b>1</b>), and a new perylenequinone, hypomycin F (<b>2</b>), were isolated from the stromata of <i>Hypocrella bambusae</i>, together with five known compounds, <b>3</b>-<b>7</b>. The structures of <b>1</b> and <b>2</b> were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of <b>1</b> was determined by electronic circular dichroism data analysis, and the absolute configurations of <b>2</b> and <b>3</b> were determined by X-ray crystallography. The axial chirality of <b>7</b> was determined by UV-induced photooxidation from <b>4</b>. Compounds <b>1</b>, <b>4</b>, and <b>5</b> showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC<sub>50</sub> values of 0.17, 0.038, and 0.12 μM. Compounds <b>4</b> and <b>5</b> were also active against live SARS-CoV-2 infection with EC<sub>50</sub> values of 0.22 and 0.21 μM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that <b>4</b> and <b>5</b> could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that <b>4</b> and <b>5</b> are potential SARS-CoV-2 entry inhibitors.