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Feb
19

Zika Virus- insights from old papers when you can get them

Hunting for information on the Zika virus has revealed several insights for me, both of them point to areas that are obvious. 1. Researchers may have missed out by not reading anything older than a few years old and 2. for all the pronouncements on data sharing and open access, still publishers have not opened up old papers.

Searching Google scholar for papers on ‘Zika virus and in vitro’ and ‘Zika virus and in vivo‘ retrieved a few papers of note. Some of which were behind a paywall (e.g. Elsevier’s journals like Antiviral Research for example). One interesting paper from 2003 by Crance et al., described interferon, ribavirin, 6-azauridine and glycyrrhizin tested against 11 flaviviruses in vero cells. As far as I can make out this is one of the few papers I have found to date that lists anything tested against Zika virus in vitro. I have access to a university library account so I was able to get this and save  $35.95. Which raises the issue, shouldn’t there be some freeing up of papers on Zika? A recent paper by Hamel et al., from 2015 also showed interferon inhibited Zika virus replication in primary skin fibroblasts, but did not cite the earlier work from 12 years earlier. So could interferons be a viable treatment for those with the virus?

The linkage between Zika virus and microcephaly was recently further cemented with a case study. But had there been any earlier signs of this possibility I wondered? Fortunately Springer made a paper by Bell, Field and Narang freely available on the ‘Zika virus infection of the central nervous system in mice‘ from 1971. This paper is telling in that inoculation of 1 day old and 5 week old mice with the virus went on to show enlargement of astroglial cells, destruction of pyriform cells of Ammons horn and clear replication of the virus occuring in neurons and astroglial cells as observed by histopathology. So for over 45 years it has been known that Zika virus could have profound CNS effects. While this study did not look at mouse fetus, it does raise concern for young infants that might be infected with the virus, could it have the same effect on the CNS as in mice? Why has this work not been highlighted earlier, it it had I think there would have been a greater urgency to develop treatments for this disease knowing that it could have developmental effects. Perhaps part of the challenge is finding this information you might say? Well there is so little literature on the virus and a few minutes spent searching can retrieve likely important papers. The challenge is still accessibility and discoverability.

 

3 comments

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  1. Rachelle Bienstock says:

    I think there are several valid approaches to targeting ZIKA which have been successful with other similar viruses. The first would be to identify broadly neutralizing antibodies for vaccine development. The second would be to target the NS5 protein C-terminal RNA-dependent RNA polymerase activity(RdRP). The third would be to target the E envelope glycoprotein to inhibit viral fusion (either through a small molecule or synthetic peptide-like drug or monoclonal antibody).
    If I were leading drug development, I would target the RNA-dependent RNA polymerase.Because host cells are devoid of this enzymatic activity, these viral polymerases represent attractive drug targets . Also the crystal structures from many viral RdRps are known, including several from the Flaviviridae family and they all possess a conserved polymerase fold despite low sequence homology. I am sure that there must be efforts to crystallize the ZIKA RdRP domain already to do drug screening. (also other drug development targeting viral RdRps has been so successful).

    1. sean says:

      Thank you Rachelle,
      Would be interested if others have started any of these. I have homology models for all these proteins and will push them out very soon.

      cheers
      Sean

  2. Al Rexroat says:

        All of this poses a challenge for U.S. health departments, which have faced pressure to reduce mosquito abatement activities amid budget cuts and increasing concerns over exposure to pesticides.

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