Discovery of Broad-Spectrum Antiviral Agents by Drug Repurposing for Rapid Response to Emergent Viral Pandemics: Building Digital Tools to Advance Translational Research

Abstract

The ongoing COVID-19 pandemic caused by the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in 2019 has highlighted urgency for a more efficient and comprehensive paradigm for antiviral development. The majority of antiviral development in the past has relied on the ‘one drug, one virus’ model, which focuses on a method of drug discovery wherein one drug exploits the biological mechanisms of one specific species of virus. However, this is an inefficient method for drug development which often dissuades many pharmaceutical companies from investing resources towards antiviral discovery. Broad spectrum antivirals agents (BSAAs) are compounds that have antiviral activity against a broad range of viruses. They have become the subject of increasing attention in antiviral development because of the advantages they confer in potentially treating multiple viral infections with one drug. Drug repurposing is also an increasingly utilized technique in antiviral development that relies on the discovery of new indications for previously developed drugs, and offers the advantage of saving time and money in the drug development process. These two approaches to antiviral drug discovery can be combined to drastically cut down on time, money, and other resource requirements of traditional drug development. If these techniques are successful, they could yield a broad arsenal of antiviral drugs that will not only help combat current viral epidemics, but also increase global preparedness for emerging viruses in the future. In this master’s thesis, I intend to describe my efforts that contributed to the building of a web-based database, DrugVirus.info, that aggregates information to promote discovery and development of novel BSAA candidates. Additionally, I will present SARS-Coronavirus-2.info, a highly accessible, multilingual website which served as a method for rapid dissemination of information in the early days of the COVID-19 pandemic. Finally, using information gathered from work on both resources, I will discuss the impact of each in the context of the emergence of SARS-CoV-2, as well as how the pharmaceutical response to COVID-19 will impact the future of BSAA development