Identification of a 3-Alkylpyridinium Compound from the Red Sea Sponge Amphimedon chloros with In Vitro Inhibitory Activity against the West Nile Virus NS3 Protease
Kremb, Stephan Georg
Kharbatia, Najeh M.
Emwas, Abdul-Hamid M.
Voolstra, Christian R.
KAUST DepartmentAnalytical Chemistry Core Lab
Biological and Environmental Sciences and Engineering (BESE) Division
Marine Science Program
Red Sea Research Center (RSRC)
Permanent link to this recordhttp://hdl.handle.net/10754/628442
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AbstractViruses are underrepresented as targets in pharmacological screening efforts, given the difficulties of devising suitable cell-based and biochemical assays. In this study we found that a pre-fractionated organic extract of the Red Sea sponge Amphimedon chloros was able to inhibit the West Nile Virus NS3 protease (WNV NS3). Using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the identity of the bioactive compound was determined as a 3-alkylpyridinium with m/z = 190.16. Diffusion Ordered Spectroscopy (DOSY) NMR and NMR relaxation rate analysis suggest that the bioactive compound forms oligomers of up to 35 kDa. We observed that at 9.4 μg/mL there was up to 40-70% inhibitory activity on WNV NS3 protease in orthogonal biochemical assays for solid phase extracts (SPE) of A. chloros. However, the LC-MS purified fragment was effective at inhibiting the protease up to 95% at an approximate amount of 2 μg/mL with negligible cytotoxicity to HeLa cells based on a High-Content Screening (HCS) cytological profiling strategy. To date, 3-alkylpyridinium type natural products have not been reported to show antiviral activity since the first characterization of halitoxin, or 3-alkylpyridinium, in 1978. This study provides the first account of a 3-alkylpyridinium complex that exhibits a proposed antiviral activity by inhibiting the NS3 protease. We suggest that the here-described compound can be further modified to increase its stability and tested in a cell-based assay to explore its full potential as a potential novel antiviral capable of inhibiting WNV replication.
CitationO’Rourke A, Kremb S, Duggan B, Sioud S, Kharbatia N, et al. (2018) Identification of a 3-Alkylpyridinium Compound from the Red Sea Sponge Amphimedon chloros with In Vitro Inhibitory Activity against the West Nile Virus NS3 Protease. Molecules 23: 1472. Available: http://dx.doi.org/10.3390/molecules23061472.
SponsorsFunding Research reported in this publication was supported by baseline research funds to Christian R Voolstra and an AEA3 award by the King Abdullah University of Science and Technology (KAUST). Acknowledgments We thank Najeh Kharbatia and Salim Sioud, technical staff at the Analytical Core Lab (ACL), as well as the Coastal and Marine Resources Core Lab (CMOR) at KAUST. We further thank Nicole de Voogd for assisting with taxonomic identification of sponge specimens.
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