Evolutionary risk assessment of European SARS-related bat coronaviruses

• Applicant: Professor Dr. Jan Felix Drexler
• Subject Area: Virology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458682210

Alike the highly pathogenic SARS-CoV and MERS-CoV, the evolutionary origins of SARS-CoV-2 lie in bats. Both SARS-CoV and SARS-CoV-2 likely originated in China in bats belonging to the genus Rhinolophus. However, a large diversity of SARS-related CoV strains exist in European rhinolophid bats. Exhaustive genomic and molecular analyses of one European SARS-related CoV by us during the last decade revealed differences in pathogenicity, including cellular entry and interferon antagonism. For all other European bat SARS-related CoVs, only small genomic fragments have been characterized. Divergent bat coronaviruses from China were found to infect primate cells via the ACE2 receptor and a large viral diversity, including multiple recombination events, was described from a single bat cave in China. Together with the independent emergence of SARS-CoV and SARS-CoV-2, this highlights the zoonotic potential of highly diverse bat SARS-related CoVs. Whether European SARS-related bat CoVs pose risks for human health remains unclear. In WP1 (Reservoir studies), we will acquire complete genome data using in solution capture-enriched high throughput sequencing (HTS) to determine up to 100 divergent SARS-related CoV genomes. In WP2 (Evolutionary analyses), we will investigate the origins and evolutionary patterns of rhinolophid SARS-related CoVs to identify macro-evolutionary patterns and SARS-related CoV strains particularly prone to hosts switching. In WP3 (In silico modeling of spike-receptor interactions) we will sequence ACE2 orthologues from different Rhinolophus bat species and other mammalian hosts and predict the capacity of spike glycoproteins of European SARS-related bat CoVs to interact with those ACE2 orthologues. The results of EURO-SARS have direct implications for risk mitigation strategies of potential future SARS-related CoV outbreaks, inform pathogenesis studies and aid adjustment of diagnostic tools, therapeutics and vaccine candidates.

• DFG Programme: Research Grants