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SARS-CoV-2 spike protein favors ACE2 from Bovidae and Cricetidae. SARS-CoV-2 causes the recent COVID-19 public health crisis. Bat is the widely believed original host of SARS-CoV-2. However, its intermediate host before transmitting to human is not clear. Some studies proposed pangolin, snake or turtle as the intermediate hosts. ACE2 is the receptor for SARS-CoV-2, which determines the potential host range for SARS-CoV-2. Based on the structural information of the complex of human ACE2 and SARS-CoV-2 RBD, we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae and Cetacea maintained the majority of key residues in ACE2 for associating with SARS-CoV-2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS-CoV-2 RBD. We found that nearly half of the key residues in turtle, snake and bird are changed. The simulated structures showed several key contacts with SARS-CoV-2 RBD in turtle and snake ACE2 were abolished. Our study demonstrated that neither snake nor turtle was the intermediate hosts for SARS-CoV-2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. Our study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS-CoV-2. This article is protected by copyright. All rights reserved.

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