Needles in a Haystack: The Search for the Next Great Antiviral

 

Research Team:  Gabrielle Gate, Egor P. Tchesnokov, and Matthias Götte

The all-too-recent COVID-19 pandemic illustrated the importance of emergency preparedness, and just how quickly a virus can get out of hand when there is a lack of effective antivirals available. Despite a death toll of over 6.5 million, only one FDA-approved drug, remdesivir, is available to treat COVID-19. While the Götte lab has previously shown that remdesivir has potent antiviral activity, they have also shown that mutations in the virus can confer resistance to remdesivir, rendering the drug ineffective. Herein lies a major challenge of the antiviral drug development pipeline: viruses evolve rapidly, and existing antivirals (if available) may not be effective against new strains that arise. As such, it is absolutely paramount to develop new antiviral drugs, and quickly. But drug development can take years, if not decades. Here we describe a high-throughput method that allows us to rapidly screen hundreds of thousands of compounds for antiviral properties against a particular virus. Compounds that show antiviral activity in these in vitro assays can then be further characterized, opening up new avenues of research into structural, mechanistic, and therapeutic studies, and ultimately lead to the development of new antiviral drugs. Our goal is to use this method to develop antiviral drugs against several viruses that the World Health Organization has identified as priority pathogens. In this way, we aim to better protect all citizens by creating more effective antivirals that are ready to use before the next virus with ‘pandemic potential’ can escalate to a global scale.

Gabrielle Gate obtained a Bachelor of Science with Specialization in Biochemistry here at the U of A in 2020, as well as a certificate in Biomedical Research. She joined the Götte lab in fall 2021 as a graduate student in the Department of Medical Microbiology and Immunology. Her thesis project focuses on identifying allosteric inhibitors of viral polymerases using high-throughput methods, with the ultimate goal of developing new antiviral drugs to treat SARS-CoV-2, as well as two hemorrhagic fever viruses: Lassa fever virus and Crimean-Congo fever virus.