For this reason, the protective effect of CQ in the murine EBOV challenge model is encouraging. None of the reported studies address the pharmacodynamics of the antiviral activity by demonstrating that the compound accumulates in the relevant tissue or compartments where the virus is replicating in vivo. Chloroquine has a large volume of distribution, which Temozolomide suggests that its rapid dissemination into extravascular tissues may impact its inhibitory activity. Clearly, the spectrum of viruses for which this class of compounds would be Reversine useful in vivo will be strongly determined by this factor, as well as by the potency of the compound itself in inhibiting specific steps in viral replication. Improvements in formulation, such as encapsulation within liposomes may also be of utility in modifying the pharmacokinetics of 
CQ in vivo. The antiviral activity of CQ may serve as an initial starting point for antiviral development through optimization of the 4AQ scaffold and by exploiting the decades of experience in toxicological investigation for this class of compounds. Significant effort has been expended in optimizing derivatives of CQ for malaria strains that have acquired resistance. By optimizing the antiviral activity of these compounds for short- or intermediate-term therapeutic dosing, it should be possible to develop analogs with entirely different properties than those required for antimalarial activity, including lower toxicity. We have successfully identified many clinically useful drugs that are potential inhibitors of bacteria and virus infection. The efficacy of lomefloxacin against BA and CQ against EBOV in vivo has not been previously reported. The ability of erythromycin to inhibit filoviruses as well as bacteria is intriguing and suggests that this drug can act not only by impacting bacterial growth but also on the cell itself, possibly by altering uptake of the pathogen. Many other pathogen-specific drugs were identified that will require evaluation in animal models. The identification of these compounds lends credence to the repurposing approach for novel drug discovery against high containment and/or biodefenserelated pathogens. The potential to reduce the time from bench to clinic is great, and accelerating this process would save lives in the event of an outbreak of any pathogen. In the past decade, Phosphatase of Regenerating Liver family members have been touted as molecular markers that significantly correlate to the ability of cancers to metastasize,,. In addition, laboratory studies indicate that PRLs are promising therapeutic targets; interfering with PRL function using antibodies and RNA interference has shown dramatic reduction in tumor formation in mice,. PRL-1 was first isolated as a novel tyrosine phosphatase that is immediately transcribed following a partial hepatectomy, continually expressed in a number of tumor cell lines and able to transform non-tumorigenic cells,. Later, PRL-2 and PRL-3 were identified by sequence analysis. Studies in cell culture indicate that exogenous expression of PRLs can induce cell proliferation,,,, migration,,, and invasiveness,,. Most significantly, constitutive expression of PRL1 and -3 enable cultured cells to form tumors when injected into mice,,. The potential of increased levels of PRLs to actively contribute to oncogenesis complements dozens of studies correlating PRL expression to tumor aggressiveness.