Lets start 2016 with a bang. Frequent Ebola collaborator Dr. Megan Coffee just pointed me to a new article in the New England Journal of Medicine that showed a ‘natural experiment’ of how fewer Ebola patients died if treated with artesunate-amodiaquine compared with artemether-lumefantrine. This is fascinating because it goes some way to verify work of another collaborator Dr Peter Madrid at SRI who showed in vitro activity of amodiaquine against Ebola virus in 2013. Yes I have written about this work before, it even lead to our own interest in Ebola in turn resulting in publications in F1000Research as a way to raise awareness of the need to find small molecules that were readily available 1, 2, 3, 4, 5.
To little avail.
I even reached out directly to Dr. Peter Jahrling at NIAID back in October 23rd 2014 in an attempt to get them to reassess the work from Peter Madrid. Our conversation is below.
Dear Dr. Jahrling,
One of my colleagues sent me the video of your talk at Johns Hopkins.
I was struck by the testing of antivirals attempting to repurpose them for Ebola and their lack of success
I was not sure if you were aware of the extensive screening in vitro of FDA approved drugs published in 2 independent studies last year. These efforts reported encouraging in vitro and in vivo data and I believe should be the starting point for more extensive followup.
In one study, the antimalarials amodiaquine and chloroquine were found to be active using in vitro cell culture assays and an in vivo mouse model (PLoS One. 8, e60579, 2013). Both drugs are cheap, generally safe, and likely readily accessible in Africa according to an experienced infectious disease Dr. I have communicated with. These compounds have also shown relatively broad activity against other viruses in vitro and in vivo in animal models (Dengue, Coronavirus OC43, SARS etc). A second study suggested selective estrogen receptor modulators clomiphene and toremifene as inhibitors of Ebola virus (Sci Transl Med. 5, 190ra79, 2013). The latter compounds are likely more accessible in the west and indicates that other FDA or EMEA approved drugs may be worth testing including those with hormonal effects.
I was not involved in any of this published work. I hope its useful.
Sincerely
Sean
October 24th 2014
Sean,
We are aware of both these studies. In fact, several of my staff members are coauthors on the SERM paper. Toremifene is one of the positive controls we use in all our drug screening protocols. I appreciate your interest.
Peter
October 24th 2014
yes I saw the video which mentioned toremifene but there was no mention of the antimalarials. You may not be aware that Peter (M) has additional replication and entry data for FDA approved drugs that has not been published yet. Perhaps he can share that with you because there are several low uM inhibitors of replication that may be useful. BTW all the 4 hits from the 2 published papers share the same pharmacophore which may hint at mechanism http://figshare.com/articles/
From talking to a clinician with experience of working in Africa, chloroquine and amodiaquine would be accessible.
Thank you for the enlightening presentation.
October 24th 2014
Sean,
Thank you for this follow-up. I am copying Gene Olinger who heads our antiviral drug testing group at the IRF in case Peter M wants to contact him or me in the future. Gene will be out of the office until next Wednesday.
Peter
There was no further communication with NIAID. I mean really why should they listen to me?
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