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