Catalyzing One Health Research on Highly Pathogenic H5N1 Avian Influenza A (HPAI H5N1) Viruses: An integrated transdisciplinary approach using translational genomics, AI-driven modeling, and phenotypic profiling

One Health surveillance and investigation of avian influenza A viruses are crucial for understanding the ecology, epidemiology, and genetics of these highly dangerous influenza viruses, so that we can predict and prevent disease spread. Although genomics has been integrated into Highly Pathogenic Avian Influenza A viruses (HPAIV) response programming, there remain several important gaps in maximizing its usefulness. Specifically, genomics could be applied to understanding the biological significance and impacts of fast-spreading mutations in the HPAIV genome on viral biology and to developing potential pharmaceutical interventions against emerging HPAIV of global concern (such as the H5N1 Bird Flu). We have assembled an inter-institutional and inter-sectorial team of virologists (Dr. François Jean, nominated principal applicant; UBC), chemists (Dr. Raymond Andersen, co-applicant; UBC), and genomics epidemiologist (Dr. Shannon Russell; co-applicant, BCCDC) who have an established track record of experience in knowledge dissemination, translational technologies, and addressing emerging viral threats. To complement this expertise and to catapult knowledge exchange between different content experts (e.g., genomics, virology), we have included non-academic collaborators-Virongy Biosciences (USA) and Thoth BioSimulations (Canada). Our expert team will develop and apply novel research platforms to translate genomic information from emerging HPAI H5N1 viruses for detailed structural analysis, rapid antiviral drug testing, and continuous information sharing with health authorities. Our One Health research platforms will create a unique, cloud-based "HPAI Data Dashboard" with risk prediction tools and visualizations of the newly identified and validated biosignatures (i.e., risk signals) to disseminate real-time critical, time-sensitive information to public health decision makers.