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Apr
05

How close were we in our predictions on the Zika structure?

Perhaps you missed it but late last week the 3.8Å resolution structure of the mature Zika virus as determined by cryo-electron microscopy was published in Science by groups at Purdue University and NIAID.

I knew it was coming since I emailed Dr. Rossman Feb 24 with our ‘homology models’ paper submitted to F1000Research and had a reply on the 26th to the effect of .. ‘we are working on it.’

Sadly our models did not get a citation even though we 1. correctly predicted a single glycosylation site at Asn154 using freely available software which they experimentally confirm and  2. we correctly predicted that the virion would closely resemble Dengue virus on the surface. Perhaps this is an oversight in the rush to get published but anyone can go to F1000Research or to our Figshare collection and compare the files and what we had written over a month earlier. Perhaps the authors can add one reference after the fact because they definitely were aware of the work based on the email. I think our little computational experiment with Zika virus may suggest that actually such approaches can do a pretty good job when all we have to work on is a sequence! That will be very useful for the next virus of interest when we know we have at least a month to wait before a cryo-EM surfaces. A month can make a big difference if you have to quickly find a potential therapeutic.

Perhaps what was missing from the Science paper was discussion of the surface charge pattern on the virus and perhaps more detail that could be gleaned from it compared to other flaviviruses. While the Science paper made little or no reference to drug discovery, certainly it will also be interesting to see how this low resolution structure compares to the homology models for glycoprotein E for docking etc. For sure there is plenty to be done as the cryo-EM structures below show immature flavivuses look similar to other immature flavivirues and mature viruses look similar to other mature flaviviruses but the devil is in the details at the molecular level and that suggests the need for unique vaccines and probably drugs too for each virus. Plenty of work ahead.

This little project so far was also a wake up call, that it does not matter how open you are, people will still not cite work you are involved with! Am I right to call this out, you decide. Moving on..

flaviviruses

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