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

J Nat Prod. 2021 Feb 26;84(2):436-443. doi: 10.1021/acs.jnatprod.0c01136. Epub 2021 Feb 9.

Abstract

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 μM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 μM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 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 4 and 5 are potential SARS-CoV-2 entry inhibitors.

MeSH terms

  • Hypocreales / chemistry*
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Perylene / analogs & derivatives*
  • Perylene / chemistry
  • Perylene / pharmacology
  • Quinones / chemistry
  • Quinones / pharmacology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / physiology
  • Virus Internalization / drug effects*

Substances

  • Naphthoquinones
  • Quinones
  • perylenequinone
  • Perylene