Abstract
Simian virus 40 large T-antigen (SV40 LT-Ag) is a 708 amino acid nuclear phosphoprotein. Among many functions of LT-Ag is its ability to perform as an ATPase-helicase, catalyzing the unwinding of viral genome during replication. The LT-Ag has been employed in the studies of helicase structure and function, and has served as a model helicase for the screening of antiviral drugs that target viral helicase. In this study, using in vitro enzyme assays and in silico computer modeling, we screened a batch of 18 fluoroquinolones to assess their potential as antivirals by virtue of their inhibition of the LT-Ag helicase. We found all fluoroquinolones to be inhibitory to the helicase activity of LT-Ag. In our docking analysis, most of these tested drugs showed similarity in their interactions with LT-Ag. Our study shows the potential of fluoroquinolones as antiviral drugs and of SV40 LT-Ag as a model protein for screening drugs against viral helicases.
Highlights
Simian virus 40 (SV40) is a small, non-enveloped DNA virus [1]
Inhibition of LT-Ag Helicase Activity by Fluoroquinolones: The LT-Ag helicase activity was measured in the presence of 0.1, 1.0,10 and 100μM fluoroquinolone
Except for Lomefloxacin and Ofloxacin, all six fluoroquinolones showed Hbond interactions with Gly445 and Glu473 in the binding pocket of LT Ag (Table2 and Figure 2). It did not form H-bond interactions, amino acid Leu440 was found in the binding pocket of all fluoroquinolones except Lome- and O-floxacin (Figure 2)
Summary
Simian virus 40 (SV40) is a small, non-enveloped DNA virus [1]. The virus’ genome comprises two sets of genes: late and early expressed [2]. In concentrations of 0.1, 1, 10 or 100 μM, were tested for their inhibition on LT-Ag helicase activity. At 100μM concentration, all drugs except Enrofloxacin, Flumiquine, Sparfloxacin and 8Quinolinol, showed 60-90% inhibition of helicase activity.
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