Evolutionary risk assessment of European SARS-related bat coronaviruses
Final Report Abstract
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. 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. 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. Whether European SARS-related bat CoVs pose risks for human health remains unclear. We acquired complete genome data of nine divergent SARS-related CoVs and investigated 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 this context we discovered two reservoir-bound SARS-related coronaviruses in which a single nucleotide exchange would predictably suffice to enable furin cleavage of the viral Spike glyocprotein, which is a hallmark of SARS-CoV-2. In addition, we can show that these viruses possess genetic features such as purine richness or RNA secondary structures, that likely facilitate genetic modifications. The results of this project contribute significantly to the biological risk assessment of the zoonotic potential of reservoir-bound coronaviruses and provide insights into the origin and natural evolution of SARS-CoV-2.
Publications
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Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses. Communications Biology, 5(1).
Sander, Anna-Lena; Moreira-Soto, Andres; Yordanov, Stoian; Toplak, Ivan; Balboni, Andrea; Ameneiros, Ramón Seage; Corman, Victor; Drosten, Christian & Drexler, Jan Felix
