Active substances: Norfloxacin
Our data further show that at the concentration tested, CQ directly perturbs virus trafficking, leading to the formation of what appear to be aggregates of accumulated virus particles. In this case, CQ appears to inhibit progression of EBOV through the cell, in addition to potential effects on proteolytic processing.
It is currently unclear which mechanism is most important for the observed effects of CQ in vitro and in vivo.
In addition to its impact on viral trafficking, CQ has been shown to interfere with viral replication by impairing the glycosylation machinery in the Golgi that would direct trafficking and maturation of nascent viral proteins.
Our results provide further evidence that nonspecific inhibitors of viral entry would be a valuable complement to the antiviral arsenal and might also be considered as elements of combination therapy with more specific inhibitors.Download MS PowerPoint Slide The practice of drug repurposing, in which a this area with the formation of disease is then identified for possibly treating a second disease, has emerged as an attractive alternative for drug discovery research. Recently, the National Center for Advancing Translational Science NCATS has invested in drug previously developed to treat one the NIH Chemical Genomic Center Pharmaceutical Collection as both an informatics and screening resource for drug repurposing research, 23 lending credence to the potential and popularity of drug repurposing.
Despite the encouraging in vitro data on the efficacy of CQ as an antiviral, previous studies that have sought to demonstrate its in vivo efficacy have been less successful.
Studies in mouse models of influenza and in hamster and ferret models of Nipah virus, have failed to demonstrate that CQ affects the duration or severity of disease.
Clinical studies of CQ monotherapy against Chikungunya, and Dengue virus show that when CQ is dosed as for antimalarial use against an established human viral infection, it does not appear to impact disease severity or time to resolution.
Importantly, the design of these studies did not address the early stages of infection.
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.
Clearly, the spectrum of viruses for which this class of compounds would be 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.
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.
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Results and Discussion Jump To Chemistry A total of 84 terfenadine-based analogues were synthesized for optimization of antimicrobial activity against S. An alternate pathway was used to synthesize analogue 1 i in which the methyl 4- 4-chlorobutanoyl benzoate 8 i was prepared according to a previously reported procedure, 29 reduced, and subjected to a Finkelstein reaction with 7 to yield the desired analogue Scheme 2.