Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, Streptomyces sp. SV 21

Abstract

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomycescavourensis SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound 4, its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS2 fragmentation pathways as well as 1H and 13C NMR spectra and found that the previously reported structure of compound 4 differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds 2, 3 and 4 revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far.

Culturable Microorganisms Associated with Sea Cucumbers and Microbial Natural Products

“…SV 21, isolated from the sea cucumber S . vastus in Lampung, Indonesia [ 72 ]. Compounds 142 – 145 exhibited antifungal activity against Mucor hiemalis , with MIC values of 16.6, 8.3, 2.1, and 16.6 µg/mL, respectively.…”

“…Compounds 143 – 145 showed pronounced antiinfectivity effects against hepatitis C virus (HCV). Compound 142 showed weak antiinfectivity effects against HCV [ 72 ].…”

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

“…Given the commonly known mechanism of antibiotic action, it is clear that the role of K + and Na + ions in RNA synthesis is irreplaceable. Currently, it is well-known that ion channels are good targets for antiviral therapies since different ions are important throughout the whole viral cycle, not only during RNA synthesis [ 91 , 92 , 93 ]. Some of the viral proteins even function as ion channels themselves [ 94 ].…”

A Soft Spot for Chemistry–Current Taxonomic and Evolutionary Implications of Sponge Secondary Metabolite Distribution

“…Since the first discovery of bioactive chemical compounds from sponges in the 1950s by Bergmann and Feeney [ 30 ], many other marine organisms (e.g., nudibranchs, algae, bacteria) became known to be producers of bioactive natural products. However, so far, sponges remain by far their most potent sources [ 31 , 32 ], although marine bacteria, especially bacteria and fungi isolated from sponges and other marine invertebrates have gained much attention as sources of novel bioactive compounds [ 33 , 34 ]. While sponge secondary metabolites serve important roles for the defense and survival of sponges, their various effects (e.g., anti-inflammatory, anti-bacterial, anti-viral, anti-platelet, anti-cancer, etc.)…”