Technology
A Structure-Based Drug Discovery Strategy Targeting Viral Replication Inhibitors
Our proprietary structural biology, enzymology and medicinal 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 unique structure-based drug discovery platform provides a 3-D structure of inhibitor complexes at near-atomic resolution and immediate insight to guide Structure Activity Relationships (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
Market-Driven Product Profiles
Patients suffering from common viral infections have few effective treatments. Some available options have characteristics that limit their market potential such as pricing, poor tolerance, inconvenient administration, ineffectiveness against some viral subtypes or resistance.
Our goal is to develop best-in-class antiviral therapies that, at minimum, have the following characteristics:
- Effective against all viral subtypes that cause disease
- High barrier to viral resistance
- Fast onset of action and/or shortened treatment time
- Good safety and tolerability profile
- Ease of administration (e.g., oral or inhaled)
Broad-Spectrum Antiviral Activity
We are designing and developing drug candidates to be effective on the broadest possible range of viruses causing the disease.
For any virus there are different strains that cause the disease, for example, the different variants that emerged during the SARS-CoV-2 pandemic. Many antiviral drugs available today are effective only against certain strains of viruses and are less effective or not effective at all against other strains. We are developing drug candidates to specifically target proteins involved in viral replication. Despite the viral strains, these replication enzymes are essentially identical (i.e., highly conserved) among all strains of a given virus. By targeting these conserved replication enzymes, our antiviral compounds are designed and tested to be effective against major virus strains. Replication enzymes are generally conserved not only among subtypes of a given virus, but also among different viruses. This creates an opportunity for the development of broad-spectrum antiviral drugs.
High Barrier to Resistance
Our focus is on targeting viral replication proteins that can overcome the obstacle of viral resistance.
Drug resistance is a major obstacle to developing effective antiviral therapies. Viruses can reproduce rapidly and in enormous quantities in infected human cells. During viral replication, random changes in the viral genome, called mutations, develop. If such a mutation occurs in a region of the viral genome that is targeted by a given 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 drug 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.
Our focus is on viral replication proteins that can overcome the obstacle of viral resistance. We identify and target critical components of viral replication proteins that are essential for function, therefore, sensitive to change. A mutation in these critical components is likely to inactivate the replication protein and, in turn, render the virus incapable of replicating. Because the mutated virus cannot propagate, it cannot effectively develop resistance to the enzyme inhibitors we employ. We test the effectiveness of our compounds against potential viral mutations and select compounds with the highest barrier to resistance.
Our technology is based on the work of our Chairman of the Board, Chief Scientific Officer and Chairman of our Scientific Advisory Board, Dr. Roger Kornberg.
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 right of RNA being transcribed by an RNA polymerase.
Leveraging Dr. Kornberg's research enables us to identify and develop new antiviral compounds through the following methods:
- Directly visualizing how viral replication enzymes work
- Identifying key parts of these enzymes to target
- Designing compounds to block the function of enzymes to prevent viral replication
- Discovering novel nucleosides and other compounds that inhibit viral replication