Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 t...Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.展开更多
基金supported by the National Key R&D Program of China(2022YFC2303401,2021YFA1300803)National Natural Science Foundation of China(32122008)+2 种基金supported by Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)fellowships from the China Postdoctoral Science Foundation(2022T150688)the Postdoctoral Science Foundation of China(2021M700161).
文摘Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.
