Axial Chiral Binaphthoquinone and Perylenequinones from the Stromata of Are SARS-CoV-2 Entry Inhibitors.

A new axial chiral binaphtoquinone, hypocrellone (), and a new perylenequinone, hypomycin F (), were isolated from the stromata of , together with five known compounds, -. The structures of and were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of was determined by electronic circular dichroism data analysis, and the absolute configurations of and were determined by X-ray crystallography. The axial chirality of was determined by UV-induced photooxidation from . Compounds , , and showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC values of 0.17, 0.038, and 0.12 μM. Compounds and were also active against live SARS-CoV-2 infection with EC values of 0.22 and 0.21 μM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that and 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 and are potential SARS-CoV-2 entry inhibitors.