PT - JOURNAL ARTICLE AU - Stephanie N. Seifert AU - Shuangyi Bai AU - Stephen Fawcett AU - Elizabeth B. Norton AU - Kevin J. Zwezdaryk AU - James Robinson AU - Bronwyn Gunn AU - Michael C. Letko TI - An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines AID - 10.1101/2021.12.05.471310 DP - 2022 Jan 01 TA - bioRxiv PG - 2021.12.05.471310 4099 - http://biorxiv.org/content/early/2022/04/01/2021.12.05.471310.short 4100 - http://biorxiv.org/content/early/2022/04/01/2021.12.05.471310.full AB - Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and −2 has resulted in the discovery of numerous animal sarbecoviruses – the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and −2, one virus, Khosta-2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2ONE SENTENCE SUMMARY European bat coronaviruses that are only distantly related to SARS-CoV-2 but use the same cell entry route, escape the immune response against SARS-CoV-2 vaccines, driving the need for broader vaccines.Competing Interest StatementThe authors have declared no competing interest.