Ferrocin A

Novel iron-containing peptide antibiotics, ferrocins A, B, C and D, have been isolated from the culture filtrate of Pseudomonas fluorescens YK-310. These antibiotics were purified by butanol extraction, followed by column chromatography using adsorption resin, silica gel and preparative reverse-phase HPLC. The structures of ferrocins were elucidated using spectroscopic and degradative methods. Ferrocins contain three hydroxamate moieties per ferric ion which forms an octahedral iron complex.

Background: Coronavirus disease 2019 (COVID-19) is caused by a novel virus that is responsible for the largest pandemic in recent times. Although numerous studies have explored methods to cope with COVID-19 and targeted drugs and vaccines have been developed, the spread of disease remains rapid due to the high infectivity and mutation capability of SARS-CoV-2, the causative virus of COVID-19. Therefore, there is an urgent necessity to seek more efficient treatments and approaches to combat the disease. Methods: In this study, molecular docking was used to predict the binding of different lipopeptides, which exhibit significant biological functions, to the RNA-dependent RNA polymerase (also known as nsp12) of SARS-CoV-2, the central component of coronaviral replication and transcription machinery. Results: The results showed that seven lipopeptides bound to nsp12 at the same location as the FDA-approved drug remdesivir, with higher affinities. Notably, iron-chelating ferrocin A (ferrocin A-iron complex [FAC]) bound to nsp12 most tightly, releasing up to 9.1 kcal mol-1 of free energy. Protein-ligand interaction analysis revealed that FAC formed four hydrogen bonds, two hydrophobic interactions, and three salt bridges with nsp12. These active amino acids are mainly distributed in the fingers and thumb subdomains of nsp12 and are highly conserved. Conclusions: Our findings suggest that the abovementioned lipopeptides can tightly bind to nsp12, and thus represent promising drug candidates for anti-coronaviral treatments with the potential to fight SARS-CoV-2.

A Gram-negative bacterium was found to produce new iron-containing peptide antibiotics, ferrocins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-310. These new antibiotics showed antibacterial activity against Gram-negative bacteria in vitro. Although the ferrocins showed similar antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa on the standard assay media, they showed strong therapeutic effects selectively against P. aeruginosa in experimentally infected mice.