Preparing for future pandemic pathogens

As illustrated by the ongoing SARS-CoV-2 pandemic and Monkeypox outbreak, viruses of animal origin can dramatically impact human life and health. Consequently, it is critical that we develop and employ surveillance tools to identify animal viruses with the potential to infect and spread in humans before a spillover event occurs. While there are several efforts underway to screen various animals, including bats and birds that are reported to harbor human-infecting viruses like SARS-CoV-1/2 as well as various influenza strains respectively, these surveillance studies predominantly rely on viral genetics and prior knowledge of animal to human virus transmission events. This approach is inherently biased towards previously observed transmission events and ignores potentially novel species that could be harboring novel viruses or serve as intermediate hosts for existing viruses.

To address this existing limitation, we are exploring whether host receptor sequence changes resulting from evolutionary arms races between viruses and their hosts can inform which animal lineages harbor viruses with the potential to infect humans. By identifying evolutionary signatures left at direct host receptor and viral entry-protein interfaces and subsequently examining whether virus-bound residues are similar to human, we intend to identify animal species that should be prioritized for virus surveillance.

In parallel, the Iwasaki Laboratory, in collaboration with the Wilen Laboratory, is using molecular biology and reverse genetics tools to study bat coronaviruses closely related to SARS-CoV-2 (SARS-like) from different sarbecovirus clades. Their main goal is to study their replication, immune response, and pathogenesis across relevant laboratory models like primary human airway epithelial cells, bat cells, and to develop biosafe rodent models to uncover the underlying molecular mechanisms that confer pandemic potential in bat SARS-like viruses. These molecular mechanisms will enable other research groups and public health organizations to risk stratify future CoV genetic variants identified in nature, and to better prepare for future pandemics.