The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses  

作　　者：Junsen Chen Junqing Sun Zepeng Xu Linjie Li Xinrui Kang Chunliang Luo Qi Wang Xueyang Guo Yan Li Kefang Liu Ying Wu 

机构地区：[1]State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology,Institute of Medical Virology,TaiKang Medical School(School of Basic Medical Sciences),Wuhan University,Wuhan,430071,China [2]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,100101,China [3]Beijing Life Science Academy,Beijing,102209,China [4]Faculty of Health Sciences,University of Macao,Macao,SAR,999078,China

出　　处：《Virologica Sinica》2024年第4期609-618,共10页中国病毒学（英文版）

基　　金：supported by the National Key R&D Program of China(2022YFC2303401,2021YFA1300803);National Natural Science Foundation of China(32122008);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).

摘　　要：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.

关 键 词：Sarbecoviruses SARS-COV SARS-CoV-2 Fox ACE2 Omicron Cryo-EM structure 

分 类 号：S85[农业科学—兽医学]