Technology

A Structure-Based Drug Discovery Strategy for Viral Replication Inhibitors

Our proprietary structural information, enzymology and nucleoside chemistry expertise enable us to develop novel antiviral agents. These technologies and our market-focused approach to drug discovery are designed to effectively create small molecule therapeutics that are safe, effective and convenient to administer.

Advantages of our Technology

Our technology provides a 3-D structure of inhibitor complexes at near-atomic resolution and immediate insight to guide SAR. This helps us identify novel binding sites and allows for a rapid turnaround of structural information through highly automated X-ray data processing and refinement.

Hepatitis C Genotypes

Broad Antiviral Activity

For any given viral disease, there are different subtypes of viruses that cause the disease. For example, there are six different types of viruses that cause hepatitis C. In hepatitis C, these subtypes are termed "genotypes." Each hepatitis C genotype is common in some parts of the world and rare in others.

Most antiviral drugs available today are only effective against certain subtypes of viruses and less effective, or not effective at all, against other subtypes. To address this problem, we develop treatments that specifically target virus molecules called replication enzymes. These enzymes are essentially identical (highly conserved) between all viral subtypes. Therefore, our antiviral compounds are designed and tested to be effective against all virus subtypes of any given virus.

High Barrier to Resistance

Viral resistance is a major obstacle to developing effective antiviral therapies that target viral molecules. Viruses reproduce rapidly and in enormous quantities. During reproduction, random variations in viral molecules called mutations spontaneously develop. If such a mutation occurs in a viral molecule that is targeted by an antiviral therapy that therapy may no longer be effective against the mutated virus. These mutated or "resistant viruses" can freely infect and multiply even in individuals who have received treatment. In some cases, resistant virus strains may even predominate. For example, in the 2009 swine influenza pandemic, the predominant strain was resistant to the best available therapies.

To overcome this obstacle, we identify and target critical components of viral replication enzymes that are crucial to the function of the enzyme and sensitive to change. Any mutation in these critical enzyme components is likely to inactivate the enzyme and, in turn render the virus incapable of replicating. We test the effectiveness of our compounds against potential viral mutations and select compounds with the highest barrier to resistance.

Market Driven Product Profiles

Patients at risk for, or suffering from viral infections have few effective antiviral treatments to choose from. Furthermore, some available treatment options have characteristics that limit their market potential. They are either priced too high, poorly tolerated, inconvenient to administer, ineffective against some viral subtypes or prone to emergence of resistance.

World Class Expertise

Our technology is based on the work of our Chief Scientific Officer, Dr. Roger Kornberg and Dr. Raymond Schinazi.

Dr. Kornberg was awarded the 2006 Nobel Prize for Chemistry for his work to visualize a replication enzyme called RNA polymerase in action. Using techniques called protein cocrystallization and X-ray crystallography, Dr. Kornberg and his colleagues generated three dimensional pictures similar to the one on the left of RNA being transcribed by an RNA polymerase.

Dr. Schinazi is a world-class expert in discovering novel nucleoside therapeutics. He founded or co-founded successful antiviral companies including Triangle Pharmaceuticals Inc., Idenix Pharmaceuticals Inc. and Pharmasset, Inc.

We are leveraging both Dr. Kornberg and Dr. Schinazi’s expertise in these methods to identify and develop new antiviral compounds. Using these methods, our scientists are able to:

  • Directly visualize how viral replication enzymes work
  • Identify key parts of these enzymes to target
  • Design compounds to block the function of these enzymes, thereby preventing viruses from replicating.
  • Discover novel nucleosides and other compounds, which inhibit viral replication