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Published: September 22, 2022
Stephanie N. Seifert, Shuangyi Bai, Stephen Fawcett, Elizabeth B. Norton, Kevin J. Zwezdaryk, James Robinson, Bronwyn Gunn, Michael Letko
Abstract
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, the RBD from 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-2
Author summary
SARS-CoV-2, the sarbecovirus behind COVID-19, emerged in the human population after cross-species transmission from an animal source. While hundreds of sarbecoviruses have been discovered, predominantly in bats in Asia, the majority are not capable of infecting human cells. Khosta-2, a sarbecovirus discovered in Russia, has been shown to interact with the same entry receptor as SARS-CoV-2. In this study, we tested how well the spike proteins from these bat viruses infect human cells under different conditions. We found that the spike from virus, Khosta-2, could infect cells similar to human pathogens using the same entry mechanisms, but was resistant to neutralization by serum from individuals who had been vaccinated for SARS-CoV-2.
Stephanie N. Seifert, Shuangyi Bai, Stephen Fawcett, Elizabeth B. Norton, Kevin J. Zwezdaryk, James Robinson, Bronwyn Gunn, Michael Letko
Abstract
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, the RBD from 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-2
Author summary
SARS-CoV-2, the sarbecovirus behind COVID-19, emerged in the human population after cross-species transmission from an animal source. While hundreds of sarbecoviruses have been discovered, predominantly in bats in Asia, the majority are not capable of infecting human cells. Khosta-2, a sarbecovirus discovered in Russia, has been shown to interact with the same entry receptor as SARS-CoV-2. In this study, we tested how well the spike proteins from these bat viruses infect human cells under different conditions. We found that the spike from virus, Khosta-2, could infect cells similar to human pathogens using the same entry mechanisms, but was resistant to neutralization by serum from individuals who had been vaccinated for SARS-CoV-2.