Tags

, , , , , ,

By Sean Ekins

Sean Ekins - finalAn idea starts out as a response to a challenge and becomes a fully-fledged scientific research project. Then before you know it, it becomes a global project involving thousands of people, and you are writing a blog about it.

It began as I pondered “how can I, a scientist without a lab” make a difference with a disease like the Zika virus infection that is garnering global attention? When all you have is a computer and your wits, it may seem an uphill battle. I knew that gathering a cadre of collaborators would provide the support needed and, more importantly, the different perspectives and experience to gather momentum and have impact. This was the start of Zika Open (as it was initially known)—an open science collaboration. It began a few months ago in January 2016, by reaching out to Priscilla Yang, Ph.D., at Harvard University, which then led me to build a homology model of the glycoprotein E—a target on the surface of Zika virus. I also connected to Carolina Horta Andrade, Ph.D., at Federal University of Goias in Brazil, with whom I had collaborated on a Dengue virus project. From there we gathered other collaborators which led to us collaboratively writing a perspective submitted to F1000Research and submitted as a preprint to Figshare.

This work grabbed the attention of scientific illustrator John Liebman, who wanted the glycoprotein structure to produce a picture of the complete virion. John was able to show the subtle differences between Dengue and Zika over a month before the eventual cryo-EM structures were published. John’s interest inspired me to try to model every protein in the virus, which I then shared with Carolina. Her group provided more exhaustive computational work on the structures, validating and analyzing them, and producing images. With Warren Lewis (University of Washington), we used online tools to predict the sites of glycosylation on the glycoprotein E, which was later shown to be correct. This work directly led to writing a second paper that we also submitted to F1000research.

Around the same time, I was active on Twitter discussing the need for work on small molecules for treating Zika and managed to get the attention of IBM’s World Community Grid (WCG) team. Discussions were centered around a large docking project with Zika proteins. I then brought in Alexander L. Perryman, Ph.D., from the Rutgers University, New Jersey, Medical School (who has worked previously with two different projects on WCG) and Carolina Horta Andrade to co-write a proposal to use the homology models for Zika and their template proteins as targets and ultimately dock >90 million compounds against them. Carolina very kindly agreed to be principal investigator (PI), and Alexander is the co-PI, along with myself. We also put together a team of experimental scientists who could ultimately help to test compounds in the lab.

Logo-openika-blackOur WCG proposal was accepted rapidly, and we then set about weeks of discussion and planning. The team grew as additional collaborators became involved to contribute both modeling and in vitro testing assistance. The biggest challenge was the project name, as after I had previously claimed the hashtag #ZikaOpen on Twitter, the World Health Organization started using it for the gathering of Zika information. So that was out of consideration. After much deliberation, we settled on OpenZika!

Now the project has kicked off, and the global community can do their bit to help. Anyone with a computer can help by donating their unused CPU cycles to run calculations that will help advance OpenZika research. Android users can use their smartphone to run calculations when it’s inactive and being recharged. There is no reason for the global community to feel powerless against the Zika virus, even without being an expert we can all do our part. I feel a sense of relief we have now initiated a study that may one day lead to a small molecule drug as a treatment. And this has all been achieved without a single penny of grant support.  The kind generosity of the scientists involved, IBM, and people like you got it up and running. We are all collaborators against Zika now. Viva OpenZika!

Acknowledgments: SE is sincerely grateful to Carolina Horta Andrade, Ph.D., and Alexander Perryman, Ph.D., for their suggestions and collaboration.

Sean Ekins, Ph.D., graduated from the University of Aberdeen, receiving his M.Sc., Ph.D., and D.Sc. in clinical pharmacology. He is CEO of Collaborations Pharmaceuticals, Inc., CEO and Co-Founder at Phoenix Nest, and CSO at the Hereditary Neuropathy Foundation and Collaborative Drug Discovery, Inc.