A novel coronavirus, SARS-CoV-2, has emerged and spread globally, causing severe respiratory illness and a pandemic. Understanding its receptor recognition mechanism is crucial for developing interventions. SARS-CoV-2 and SARS-CoV use the human ACE2 receptor for entry. The study determines the crystal structure of the SARS-CoV-2 spike protein's receptor-binding domain (RBD) in complex with ACE2, revealing structural differences that enhance ACE2 binding. The SARS-CoV-2 RBD has a more compact conformation and stabilizes two virus-binding hotspots at the RBD-ACE2 interface, increasing binding affinity. RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses ACE2 as a receptor, suggesting potential bat-to-human transmission. Structural analysis shows that the SARS-CoV-2 RBD has evolved to better recognize ACE2, with key residues contributing to this enhanced binding. The study also demonstrates that RaTG13 can bind to human ACE2, supporting the idea that SARS-CoV-2 may have evolved from bat coronaviruses. The findings provide insights into the molecular basis of SARS-CoV-2 receptor recognition and guide the development of vaccines and antiviral strategies targeting ACE2 interactions. The study highlights the importance of receptor recognition in viral infectivity and host range, emphasizing the need for targeted interventions. The structural and biochemical data confirm that SARS-CoV-2 has a higher ACE2-binding affinity than SARS-CoV, which may facilitate its transmission from bats to humans. The research also explores the role of intermediate hosts, such as pangolins, in the transmission of SARS-CoV-2. Overall, the study provides critical information for understanding the receptor recognition mechanism of SARS-CoV-2 and informs strategies for combating the pandemic.A novel coronavirus, SARS-CoV-2, has emerged and spread globally, causing severe respiratory illness and a pandemic. Understanding its receptor recognition mechanism is crucial for developing interventions. SARS-CoV-2 and SARS-CoV use the human ACE2 receptor for entry. The study determines the crystal structure of the SARS-CoV-2 spike protein's receptor-binding domain (RBD) in complex with ACE2, revealing structural differences that enhance ACE2 binding. The SARS-CoV-2 RBD has a more compact conformation and stabilizes two virus-binding hotspots at the RBD-ACE2 interface, increasing binding affinity. RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses ACE2 as a receptor, suggesting potential bat-to-human transmission. Structural analysis shows that the SARS-CoV-2 RBD has evolved to better recognize ACE2, with key residues contributing to this enhanced binding. The study also demonstrates that RaTG13 can bind to human ACE2, supporting the idea that SARS-CoV-2 may have evolved from bat coronaviruses. The findings provide insights into the molecular basis of SARS-CoV-2 receptor recognition and guide the development of vaccines and antiviral strategies targeting ACE2 interactions. The study highlights the importance of receptor recognition in viral infectivity and host range, emphasizing the need for targeted interventions. The structural and biochemical data confirm that SARS-CoV-2 has a higher ACE2-binding affinity than SARS-CoV, which may facilitate its transmission from bats to humans. The research also explores the role of intermediate hosts, such as pangolins, in the transmission of SARS-CoV-2. Overall, the study provides critical information for understanding the receptor recognition mechanism of SARS-CoV-2 and informs strategies for combating the pandemic.