The Adamantane-Derived Bananins Are Potent Inhibitors of the Helicase Activities and Replication of SARS Coronavirus

Department of Biochemistry, University of Hong Kong, Pokfulam, Hong Kong, China.
Chemistry & Biology (Impact Factor: 6.65). 04/2005; 12(3):303-11. DOI: 10.1016/j.chembiol.2005.01.006
Source: PubMed

ABSTRACT Bananins are a class of antiviral compounds with a unique structural signature incorporating a trioxa-adamantane moiety covalently bound to a pyridoxal derivative. Six members of this class of compounds: bananin, iodobananin, vanillinbananin, ansabananin, eubananin, and adeninobananin were synthesized and tested as inhibitors of the SARS Coronavirus (SCV) helicase. Bananin, iodobananin, vanillinbananin, and eubananin were effective inhibitors of the ATPase activity of the SCV helicase with IC50 values in the range 0.5-3 microM. A similar trend, though at slightly higher inhibitor concentrations, was observed for inhibition of the helicase activities, using a FRET-based fluorescent assay. In a cell culture system of SCV, bananin exhibited an EC50 of less than 10 microM and a CC50 of over 300 microM. Kinetics of inhibition are consistent with bananin inhibiting an intracellular process or processes involved in SCV replication.

Download full-text


Available from: Andreas J Kesel, Sep 27, 2015
41 Reads
    • "dsDNA unwinding activity of the protein was measured by a fluorometric assay based on the FRET from the Fluorescein to the TAMRA (Fig. 4A). A similar approach for the helicase activity assay has been reported recently in the HCV helicase and the SCV helicase [7] [24]. Previously, it has been shown that the SCV helicase requires 5 0 -overhang of the dsDNA substrate for its 5 0 to 3 0 directionality in unwinding [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent outbreak of Severe Acute Respiratory Syndrome (SARS) that caused almost 800 victims requires a development of efficient inhibitor against SARS coronavirus (SCV). In this study, RNA aptamers against SCV NTPase/Helicase (nsP10) were isolated from RNA library containing random sequences of 40 nts using in vitro selection technique. Nucleotide sequences of enriched RNA aptamer pool (ES15 RNA) contain AG-rich conserved sequence of 10-11 nucleotides [AAAGGR(G)GAAG; R, purine base] and/or additional sequence of 5 nucleotides [GAAAG], which mainly reside at the loop region in all the predicted secondary structures. Isolated RNAs were observed to efficiently inhibit double-stranded DNA unwinding activity of the helicase by up to approximately 85% with an IC(50) value of 1.2nM but show a slight effect on ATPase activity of the protein in the presence of cofactor, poly (rU). These results suggest that the pool of selected aptamers might be potentially useful as anti-SCV agents.
    Biochemical and Biophysical Research Communications 03/2008; 366(3):738-44. DOI:10.1016/j.bbrc.2007.12.020 · 2.30 Impact Factor
  • Source
    • "Forward and reverse primers (final concentration 900 nM) and the fluorescent probe (final concentration 250 nM) were mixed with Master Mix (ABI, USA) and real-time quantification was carried out using an ABI7900 Sequence Detection System. The PCR conditions were: 50 °C for 5 min, 95 °C for 10 min, then 40 cycles of 95 °C for 15 sec and 61 °C for 1 min [28] [41]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: SARS-associated coronavirus was identified as the etiological agent of severe acute respiratory syndrome and a large virus pool was identified in wild animals. Virus generates drug resistance through fast mutagenesis and escapes antiviral treatment. siRNAs targeting different genes would be an alternative for overcoming drug resistance. Here, we report effective siRNAs targeting structural genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral kinetics. We also showed the synergistic effects of two siRNAs targeting different functional genes at a very low dose. Our findings may pave a way to develop cost effective siRNA agents for antiviral therapy in the future.
    FEBS Letters 06/2006; 580(10):2414-20. DOI:10.1016/j.febslet.2006.03.066 · 3.17 Impact Factor
  • Source
Show more