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Feb
11

A passion for Zika: does anyone want to find an antiviral?

What gets your heart beating fast? For some it is making science progress as fast as they can because life is too short. For me it gets into something totally new and seeing how quickly you can contribute and collaborate with others. How fast can we bring scientists together to do something? I would argue it can happen within days if there is a motivation.

Our open Zika virus project resulted in an Opinion piece written in about a week using GoogleDocs with contributions from Megan Coffee (while in Africa), Carolina Andrade, Eugene Muratov and Lucio Freitas-Junior (all in Brazil) Daniel Mietchen, Jair Siqueira-Neto, Antony Williams, Thomas Stratton and Joel Freundlich and myself in the US . As soon as it was submitted online it was uploaded to Figshare along with supplemental data including a homology model of the glycoprotein. The subsequent edited version was also uploaded. Several scientists were also involved in putting structures of Dengue virus inhibitors together and on Wikidata including Tom, Daniel  and Egon Willighagen. Many others provided information or comments by Twitter or emails so a big thanks to them (hopefully I captured everyone in the acknowledgements). The upshot was that we have a group in Brazil working on the assay to screen compounds we proposed. Two days ago the opinion we submitted to F1000Research went live on the website. The same day a press release came out for their arbovirus portal.  The Opinion was also added to Kudos and enriched.

But that is pretty much how it happened, we were working round the clock to write something. Imagine if we already had a Zika assay up and going we could have been predicting compounds and getting them tested as well. Instead we have to wait. Hold on you say, why are you working on small molecules when 99.99% of the press currently is talking about vaccines?  Simply we think based on past experience that we already may have an approved drug that could have antiviral activity against Zika. Therefore theoretically it could come to the clinic much faster. Consistently I am seeing discussion of vaccines and funding of such work and yet nothing on small molecules.

As we point out in the Opinion piece for sure before the Ebola virus broke out there was enough evidence in the literature that some antimalarial drugs such as amodiaquine being active against it. In some clinics in Africa patients were on antimalarials. A recent study even showed the differences between antimalarials used in a ebola clinic with aretsunate-amodiaquine use increasing survival.  Just imagine if those with Ebola could have been given amodiaquine, possibly 1000’s of lives could have been spared. Obviously Zika is NOT ebola, but shouldn’t we be thinking about antivirals to slow the spread of the disease which is already affecting millions in Brazil alone? We are not in the position of having several screens with FDA drugs published as we were with ebola.  The latest NIAID notice does not mention small molecule work. Sure there is an awful lot about the virus we do not understand, it seems clear it reaches the fetal brain but we do not understand how it causes microcephaly.

So how do we get more scientists involved in finding an antiviral? An opinion, a press release, tweets, emails to some program managers at NIAID and to different scientists seems to not even dent the public discussion. I think its time for a bit of objective discussion about what is possible in the short versus long term. Viruses like HIV, HCV etc consume the majority of funding from NIH, companies etc and yet emerging viruses only see money and research when they explode. This is all wrong. We need to understand the viruses that are not on the radar. We need assays for them so that we can screen compounds and find antivirals. The ability to do some work computationally is also something we pointed to that can be undertaken quickly, but we need to be able to test compound ultimately. I think we will be able to identify an antiviral far faster than a vaccine.

I believe that we have to ask otherwise nothing will happen. So far we asked for a channel for Zika and F1000Research obliged. We asked for publishers to open up their papers and several did. Though I do not think everyone is responding to what we write!

3 comments

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  1. Gary says:

    Perhaps Arbidol would work?
    http://arbidol.info

  2. Jill Glasspool Malone says:

    BTW – NIH refuese to fund antiviral research, they have blocked BARDA from funding antiviral research. Why? Because the US Gov has decided that a vaccine is the solution (which it isn’t) and made the decision early on that the first priority was to fund vaccine research and diagnostics. So, we literally have clinical research protocols, drugs, FDA involvement and no way to capitalize these trials. It is shocking. We can not get the press interested in writing a story. We also wrote about our findings in Feb in PLoS NTD – still no one wants to actually read the science.

  3. Rachelle says:

    There are already several published studies of designed nucleoside (antivirals) against Zika.:

    (1) Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJF, Neyts J (2016) The Viral Polymerase Inhibitor 7-Deaza-2’-C-Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLoS Negl Trop Dis 10(5): e0004695. doi:10.1371/journal.pntd.0004695

    (2) Journal of Infectious Diseases Advance Access published May 27, 2016
    Nucleoside inhibitors of Zika virus
    Luděk Eyer1, Radim Nencka2, Ivana Huvarová1, Martin Palus1,3, Maria Joao Alves4, Ernest A. Gould5, Erik De Clercq6, Daniel Růžek1,3,*
    Journal of Infectious Diseases Advance Access published May 27, 2016

    (3) An all-atom, active site exploration of antiviral drugs that target Flaviviridae
    polymerases
    James J. Valdésa,b#, Victor A. Gilc, Philip T. Butterilld and Daniel Růžeka,b,d 5 (J Gen Virology, In press)

    (4) The BioCryst Pharm drug is receiving significant testing against Zika…
    Extended Data Figure 3: Efficacy of BCX4430 in
    mouse disease models.
    From Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430
    Travis K. Warren, Jay Wells, Rekha G. Panchal, Kelly S. Stuthman, Nicole L. Garza, Sean A. Van Tongeren, Lian Dong, Cary J. Retterer, Brett P. Eaton, Gianluca Pegoraro, Shelley Honnold, Shanta Bantia, Pravin Kotian, Xilin Chen, Brian R. Taubenheim, Lisa S. Welch, Dena M. Minning, Yarlagadda S. Babu, William P. Sheridan & Sina Bavari
    Nature 508, 402–405 (17 April 2014) doi:10.1038/nature13027

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