Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus caused the novel coronavirus disease-2019 (COVID-19) affecting the whole world. Like SARS-CoV and MERS-CoV, SARS-CoV-2 are thought to originate in bats and then spread to humans through intermediate hosts. Identifying intermediate host species is critical to understanding the evolution and transmission mechanisms of COVID-19. However, determining which animals are intermediate hosts remains a key challenge. Virus host-genome similarity (HGS) is an important factor that reflects the adaptability of virus to host. SARS-CoV-2 may retain beneficial mutations to increase HGS and evade the host immune system. This study investigated the HGSs between 399 SARS-CoV-2 strains and 10 hosts of different species, including bat, mouse, cat, swine, snake, dog, pangolin, chicken, human and monkey. The results showed that the HGS between SARS-CoV-2 and bat was the highest, followed by mouse and cat. Human and monkey had the lowest HGS values. In terms of genetic similarity, mouse and monkey are halfway between bat and human. Moreover, given that COVID-19 outbreaks tend to be associated with live poultry and seafood markets, mouse and cat are more likely sources of infection in these places. However, more experimental data are needed to confirm whether mouse and cat are true intermediate hosts. These findings suggest that animals closely related to human life, especially those with high HGS, need to be closely monitored.
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