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Structural Basis for HCV RNA Replication

and Inhibition by Sofosbuvir


Date: December 8, 2015 (60 minutes)

Featured Speaker:

The hepatitis C virus (HCV) can cause chronic liver disease and is the major cause of liver transplantation in the US. Recently, the nucleotide analog inhibitor sofosbuvir was approved by the FDA for treatment of chronic HCV (N. Engl. J. Med. 2013, 368, 34). Sofosbuvir is incorporated into the replicating RNA genome via the viral RNA-dependent RNA polymerase (RdRp) and blocks the incorporation of additional nucleotides thereby inhibiting HCV genomic replication.

To understand on the atomic level how the HCV RdRp replicates the HCV genome and how it recognizes nucleotide analog inhibitors, investigators at Beryllium and Gilead Sciences determined crystal structures of stalled ternary complexes of HCV polymerase in complex with RNA primer-template pairs and nucleotides such as native substrates and nucleotide analog inhibitors. The findings of this collaboration were published Science earlier this year (Appleby, T.C. et al. Science, 2015, 347, 771).

This webinar will focus on how the HCV RNA polymerase replicates the HCV RNA genome starting with basic biology continuing through Beryllium's structural mechanistic studies with native substrates and nucleotide analog inhibitors such as sofosbuvir.

Keywords: FDA, RNA, Hepatitis C Virus


    Thomas E. Edwards, Beryllium Discovery Corp.

    Thomas E. Edwards, Vice President of Structural Biology, Beryllium Discovery Corp.

    With over a decade of industry expertise, Thomas has been at the forefront of numerous, successful structure determination research collaborations, including hepatitis C virus (HCV), oncology and diabetes targets. Prior to joining Beryllium, he was a crystallographer and senior research scientist at the Seattle Structural Genomics Center for Infectious Disease (SSGCID). Thomas has deposited more than 200 crystal structures into the international Protein Data Bank and has published 50 peer-reviewed journal articles. He obtained a bachelor’s degree in chemistry from the University of Puget Sound and a doctorate in chemistry from the University of Washington, and was a Damon Runyon Postdoctoral Fellow at the Fred Hutchinson Cancer Research Center.


    Any company that is in the pre-clinical drug discovery stage such as:

    • Target Selection
    • Discovery & Screening
    • Lead Selection
    • Lead Optimization
    • Pre-Clinical Development

    Research and Development groups of all levels, from Research Scientists to Director and/or C-level executives.



    Beryllium is shaping the future of collaborative drug discovery. Our proven teams of drug discovery professionals are passionate about unlocking the therapeutic potential of both genetically- and clinically-validated drug targets, as well as developing new therapeutic modalities. We work in partnership with our clients to address the most difficult scientific and business challenges facing drug discovery, and to ultimately enable transformational health care outcomes.

    We enable novel drug discovery by applying structural and functional biology-centric processes and platforms. Our goal is to deliver validated starting points for drug development programs, and our teams of pharma industry veterans are applying multidisciplinary knowledge to tackle the most promising therapeutic targets.

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