The article reviews the epidemiology, pathogenesis, prevention, and treatment of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It highlights the pivotal role of spike proteins (S proteins) in viral entry and pathogenesis, and discusses the development of animal models that recapitulate these diseases. The SARS-CoV and MERS-CoV S proteins are trimeric glycoproteins that play crucial roles in viral infection. The article also explores the potential therapeutic targets and strategies, including vaccines and therapeutics based on the S protein. Despite extensive research, no specific treatments are available for these viruses, and further studies are needed to identify appropriate therapeutic targets. The development of stable and reproducible animal models, particularly in non-human primates, is essential for advancing the understanding and management of SARS-CoV and MERS-CoV. The lessons learned from the outbreaks of SARS and MERS provide valuable insights for future emerging infectious diseases.The article reviews the epidemiology, pathogenesis, prevention, and treatment of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It highlights the pivotal role of spike proteins (S proteins) in viral entry and pathogenesis, and discusses the development of animal models that recapitulate these diseases. The SARS-CoV and MERS-CoV S proteins are trimeric glycoproteins that play crucial roles in viral infection. The article also explores the potential therapeutic targets and strategies, including vaccines and therapeutics based on the S protein. Despite extensive research, no specific treatments are available for these viruses, and further studies are needed to identify appropriate therapeutic targets. The development of stable and reproducible animal models, particularly in non-human primates, is essential for advancing the understanding and management of SARS-CoV and MERS-CoV. The lessons learned from the outbreaks of SARS and MERS provide valuable insights for future emerging infectious diseases.