Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study

Mar Drugs. 2022 Feb 28;20(3):179. doi: 10.3390/md20030179.

Abstract

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.

Keywords: Aspergillus niger; Aurasperone A; Mpro; Phallusia nigra; Rubasperone B; SARS CoV-2; antiviral; in silico.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Aspergillus niger / chemistry
  • Chlorocebus aethiops
  • Chromones / isolation & purification
  • Chromones / pharmacology*
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Coronavirus 3C Proteases / metabolism
  • Coronavirus Papain-Like Proteases / metabolism
  • Coronavirus RNA-Dependent RNA Polymerase / metabolism
  • Molecular Docking Simulation
  • Protease Inhibitors / isolation & purification
  • Protease Inhibitors / pharmacology*
  • RNA Helicases / metabolism
  • SARS-CoV-2 / drug effects*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells

Substances

  • Antiviral Agents
  • Chromones
  • Protease Inhibitors
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • remdesivir
  • Adenosine Monophosphate
  • aurasperone A
  • Coronavirus RNA-Dependent RNA Polymerase
  • Coronavirus Papain-Like Proteases
  • papain-like protease, SARS-CoV-2
  • Coronavirus 3C Proteases
  • RNA Helicases
  • Alanine