Coronaviruses (CoVs), once considered harmless to humans, have gained global attention due to outbreaks caused by SARS-CoV and MERS-CoV. These viruses, which cross the species barrier, caused severe respiratory infections with high mortality rates. This review summarizes the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, focusing on their spike proteins (S proteins), which play a critical role in viral entry and infection. The study compares current animal models for these viruses, highlighting the importance of host receptors in determining viral tropism and pathogenicity. It also discusses the need for further research to understand viral mechanisms, develop effective animal models, and create countermeasures against these emerging coronaviruses. The S protein is a key therapeutic target, with various vaccines and therapeutics based on it being explored. Despite progress, challenges remain in developing effective treatments and vaccines, particularly for MERS-CoV. Animal models, especially in non-human primates, are crucial for studying viral pathogenesis and testing potential therapies. The role of host receptors, such as ACE2 and DPP4, in determining viral infection and disease severity is emphasized. The review concludes that continued research is essential to improve public health preparedness against SARS-CoV, MERS-CoV, and future emerging coronaviruses.Coronaviruses (CoVs), once considered harmless to humans, have gained global attention due to outbreaks caused by SARS-CoV and MERS-CoV. These viruses, which cross the species barrier, caused severe respiratory infections with high mortality rates. This review summarizes the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, focusing on their spike proteins (S proteins), which play a critical role in viral entry and infection. The study compares current animal models for these viruses, highlighting the importance of host receptors in determining viral tropism and pathogenicity. It also discusses the need for further research to understand viral mechanisms, develop effective animal models, and create countermeasures against these emerging coronaviruses. The S protein is a key therapeutic target, with various vaccines and therapeutics based on it being explored. Despite progress, challenges remain in developing effective treatments and vaccines, particularly for MERS-CoV. Animal models, especially in non-human primates, are crucial for studying viral pathogenesis and testing potential therapies. The role of host receptors, such as ACE2 and DPP4, in determining viral infection and disease severity is emphasized. The review concludes that continued research is essential to improve public health preparedness against SARS-CoV, MERS-CoV, and future emerging coronaviruses.