Robert Stratford Slides

Robert Stratford Video

Veronika Zarnitzyna Slides

Veronika Zarnitzyna Video

Robert Stratford Abstract: Drug development is a complex, multi-dimensional, process. It is an expensive process, typically requiring investment of > $1 billion dollars, and requiring several years from target identification and molecular scaffold (lead) selection, to eventual clinical development, the latter itself also a multi-year process. Owing to its complexity, drug development is a risky undertaking. In the past two decades, application of modeling and simulation approaches along the continuum of lead selection -> lead optimization -> preclinical candidate development -> clinical development -> regulatory approval has reduced risks and improved efficiency of this multi-phasic and -dimensional process. This brief presentation will present an overview of key modeling and simulation platforms that drive drug discovery and development. Attention will be given to 1) how models improve translational fidelity from pre-clinical experimental models, and 2) how they inform clinical trial design.

Veronika Zarnitzyna Abstract:  We will consider mathematical models of immune response to viral infections.  Some viruses (e.g. influenza) cause acute infection, some (e.g. HIV, herpesviruses such as CMV and EBV) results in persistent infection and some (hepatitis C and hepatitis B) may generate both outcomes in immune-competent humans. Considerable evidence has shown that differential immune response is a major factor in disease outcome in many viral infections. What features of the virus and which factors of the immune system (both innate and adaptive) affect the outcome? What contributes to the heterogeneity in the outcome? Is it possible that SARS-CoV-2 establishes a persistent infection in a fraction of otherwise healthy (at the moment of virus introduction) people? Are long-haulers dealing with organ damage after virus clearance or with low-grade reactivation of the virus? The inherent complexity of the immune system requires modeling approaches in order to reveal the molecular and cellular mechanisms that promote unhealthy or non-optimal immune responses. Moreover, the models will be valuable for expediting the discovery and optimization of immunomodulatory treatments of virus infection.