Research Highlights

Next Steps for Exceptional NBCR High School Student: Finding New Anti-flu Compounds and Publishing His First Peer-reviewed Paper – as First Author

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Figure 1: Eric Chen, grand prize winner of the fall 2013 Google Science Fair.

By comparison with his peers, Eric Chen might be considered a veteran researcher. Currently a senior at Canyon Crest High School in northern San Diego County, he has already worked for two years in several laboratories – both computational and bench science – at UCSD and The Scripps Research Institute. “I’m lucky to have the opportunity,” says Chen, “to hop from one lab to another running computations, then validating the results in the biology lab, then doing more computational or crystal structure analysis.”

Chen says he’s always been curious: “When I was younger, science seemed to have all the answers to my questions. But as I got older, I began to appreciate how much we don’t know about the world and how, by doing research, we can find the answers.”

Finding a research framework was going to prove critical to focus his curiosity. After seeing an e-mail regarding the 2012 NBCR Summer Institute, Chen approached Rommie Amaro to participate. (Amaro is NBCR director and a professor in the UCSD Department of Chemistry & Biochemistry.) His was an unusual request because the institute is generally a forum for graduate students and postdocs. But, as experience would prove, Chen is an unusual student, and he’s quick to point out how much he gained from the experience. “I was new to computational research,” he says, “and the institute provided an overview of the field and training in the software tools available.”

His current focus: Identifying effective small-molecule antivirals to counteract the flu. “I got interested in this topic when the swine flu hit in 2009,” says Chen. “I hadn’t realized how dangerous the flu was. Since then I’ve followed what new strains are emerging on the news. Some are very close to going pandemic, but we lack preparation to deal with them.”

Statistics show that the flu sickens three to five million people and leads to a half million deaths each year around the world. And, while vaccination can work effectively in healthy adults, there is typically a six-month gap between the time a new viral strain is identified and an effective vaccine developed and disseminated. Moreover, emerging resistance is providing a challenge to the long-term effectiveness of some anti-flu drugs, underscoring the need for new therapies and possibly new approaches to homing in on effective therapies.

Chen found a mentor for his research project in Rob Swift, a postdoctoral researcher (and co-author on the resulting publication). “Eric was interested in computer-aided drug discovery, one of the tracks he attended at the NBCR Summer Institute,” says Swift. “I helped him determine the approach, choose the most useful tools, develop his pharmacophore model, and write the provisional patent application.”


Figure 2: Endonuclease shown with a small molecule (green, red, and blue) determined in the study to inhibit its ability to replicate.

In computational chemistry, pharmacophore models are used to define essential features of molecules with the same biological activity. Such a model can then be used to search a database of chemical compounds for molecules with those same features.

Chen stepped up the computational experience he gained from the NBCR Summer Institute to apply the power of a supercomputer to his project. Using a process called virtual screening, he computationally assessed a half million potential small-molecule compounds to identify those with characteristics similar to those in compounds known to inhibit activity of the protein influenza endonuclease required for replication of the virus. The screen did two things: It identified compounds likely to be active and eliminated those that had undesirable properties like poor solubility and high toxicity.

Chen’s computational work produced a list of 237 candidates that could be considered leads for new anti-flu drugs. Then he tested them biologically in the lab to determine which effectively deactivated the flu virus. In general, he found good agreement between his computational predictions and laboratory analysis. Out of the 237 potential compounds, he identified 16 new inhibitors; of those two had negligible cell toxicity.

As his work was progressing, Chen submitted it under the name “Taming of the Flu” to the fall 2013 Google Science Fair. Not only did he win in his age group division (17-18 year olds) but he was named the grand prize winner of the entire competition, besting thousands of competitors from 120 countries. Earlier in the year, he also won first place in the Microbiology Division of the Intel International Science and Engineering Fair, competing against 1,600 other students.

To be sure, winning among his peers was one thing. But Chen also wanted to establish his credentials with professional scientists. So with encouragement from his faculty colleagues, he became the lead author of “Computation-Guided Discovery of Influenza Endonuclease Inhibitors,” submitted and accepted by the peer-reviewed journal ACS Medicinal Chemistry Letters (see citation below).

“Eric’s publication presented five new molecular scaffolds that are active against this new target in flu,” says Amaro who also served as his mentor. “His work could be important for developing new drugs that work against resistant or newly emerging strains of flu.”

This research has already been patented, and Chen is hopeful it will be used to focus future drug discovery and design efforts. As for his own plans, he says he’s likely to focus on computer science, biology, and applied math with professional interests in research, teaching, and entrepreneurship.

“Eric is a terrifically talented young scientist who has tremendous drive and passion,” says Amaro. “Part of what makes Eric so special is that he is both deeply curious and, perhaps just as important, courageous,” she said. “He is absolutely fearless when it comes to doing exciting new things, and that has made all the difference in his work.”

References: 

  1. 1. Chen, Eric, Robert V. Swift, Nazilla Alderson, Victoria A. Feher, Gen-Sheng Feng, and Rommie E. Amaro, Computation-Guided Discovery of Influenza Endonuclease Inhibitors, ACS Medicinal Chemistry Letters, Article ASAP, DOI: 10.1021/ml4003474, http://pubs.acs.org/doi/abs/10.1021/ml4003474
  2. 2. http://googleblog.blogspot.com/2013/09/and-winner-of-2013-google-science-fair.html

Researchers: Eric Chen, Robert V. Swift, Nazilla Alderson, Victoria A. Feher, Gen-Sheng Feng, and Rommie E. Amaro

Figure 1: Eric Chen, grand prize winner of the fall 2013 Google Science Fair.
Figure 2: Endonuclease shown with a small molecule (green, red, and blue) determined in the study to inhibit its ability to replicate.