|Title||Alkaloids from the sponge Stylissa carteri present prospective scaffolds for the inhibition of Human Immunodeficiency Virus 1 (HIV-1)|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||O'Rourke A., Kremb S., Bader T.M, Helfer M., Schmitt-Kopplin P., Gerwick WH, Brack-Werner R., Voolstra C.R|
|Type of Article||Article|
|Keywords||drug discovery; HIV-1; hymenialdisine; kinases; marine; marine bioprospecting; natural-product; Red Sea; reverse transcriptase; Stylissa carteri|
The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%-40% inhibition of HIV-1 at 3.1 M and 13 M, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 M with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 M. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery.
|Short Title||Mar. Drugs|