Tuesday, October 21, 2014

Ebola virus is no match for feminine power

These days everyone is talking about Ebola. I remember reading news article in early 2014 discussing spread of Ebola in West African countries. It was very puzzling since such highly virulent infectious agents are usually self-limiting. Something is certainly different this time. It appears it now developed a mutation allowing prolonged incubation time.

It is obvious Ebola is new virus for human immune system and most likely there is no natural (genetic) immunity against it. It means that adaptive immune system goes into overdrive because innate system lacks genetic memory of Ebola and is unable to properly instruct effector T and B cells. In this situation, survival depends on presence antibody or T cells cross-reactive to environmental microbes or host commensals.

However, sometimes protection against virulent infections can come from unexpected corner. Here is such example for Ebola. While researching Ebola publications prior to 2014 outbreak, I came across two research articles about Ebola that immediately caught my attention.

These papers were published in April-June 2013 by two independent groups. One was published in Plos One (A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents), and another in Sci Transl Med (FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection). Only similarity was that some of the authors (but not the same authors) from each group were from U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)

Basic idea of the studies were to screen FDA-approved drugs to see if any of the drugs would protect against category A biological threat agents, like Ebola. This is called drug re-purposing and has many advantages considering the fact that lengthy human safety studies have already been conducted on such medications.

Using both in vitro cell culture assay or in vivo mouse models, both studies independently showed that FDA-Approved Selective Estrogen Receptor Modulatorstoremifene or clomiphene, blocked Ebola virus host cell entry capacity by 97% and protected >50% (90% protection in clomiphene group) of infected mice (100% death in untreated group).  

Sci Transl Med 19 June 2013
Fig. 4

Interestingly, the authors think this protection is estrogen-receptor independent, basically meaning that response appeared to be an off-target effect, completely unexpected. 

It maybe time for FDA to have a quick look for such data. It may indeed provide quick and safe alternatives (to vaccines) in times of uncertainty.

David Usharauli

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