Repurposing Drugs to Fight Zika: Putting it into Context

Bursting through the almost continual parade of negative Zika headlines was news that 3 drugs -- one of which (niclosamide) was once FDA approved for another indication have the potential to combat this virus and its severe complications. This study was done in vitro in a laboratory setting and is unequivocally promising. The discoveries center on two drugs with antiviral effects and one which acts as a neuroprotectant. However, as I elaborated on in this interview with Healthday, there several important questions and caveats needed to put this finding in the proper context, two of which I discuss below.

1. In vitro needs to become in vivo: The most obvious next step to be taken with this finding is to see if it holds up--and provides a clinically meaningful benefit--in animal models. Can effective doses be achieved? How robust is the response in an animal model? Do they cross the placenta? Are they safe in pregnancy (at least niclosamide is)? These are the types of questions that would be pursued with an animal model and provide an ability to gauge the feasibility of these drugs as actual treatment options.

2. Concept of Operations: Anytime a new countermeasure is being evaluated for its use in the treatment, prevention, or control of an infectious disease the use case for how it is to optimally used must be part of the discussion. With Zika, an antiviral strategy is difficult for several reasons including, chiefly, the fact that the vast majority of people do not know they are infected and therefore wouldn't be prompted to seek treatment. Secondly, Zika is largely a fleeting virus that comes and goes and in that short process, in certain circumstances, causes fetal harm in pregnant women. Can pharmaceutical intervention occur quickly enough?  Can these compounds make an actual impact on complications? 

If I were to think of a possible concept of operations it would have to center around using these drugs prophylactically to prevent or blunt infection -- if the drugs have that ability in vivo. For only with high drug levels in one's body pre-infection could one have a good chance at preventing the virus from taking hold, spreading to the fetus, or causing other complications like Guillain-Barre Syndrome.

Overall, the repurposing of existing drugs in the face of an emerging infectious disease outbreak is a major effort that provides the fastest path forward to developing new countermeasures. This is especially true if the drug being repurposed has already been FDA approved for another indication such as niclosamide was. When an already approved drug can be used "off label" for a new clinical problem, the burden of funding large clinical trials and complying with FDA regulations is substantially lower.

Until a vaccine is available for Zika, it will be worthwhile to explore potential uses of antiviral therapy but building a concept of operations in which these compounds can be used optimally is essential.