The study investigates the structural basis of receptor recognition by SARS-CoV-2, a novel coronavirus that has emerged and rapidly spread, causing the COVID-19 pandemic. The virus recognizes angiotensin-converting enzyme 2 (ACE2) as its receptor, similar to SARS-CoV. The researchers determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein complexed with ACE2. They found that the SARS-CoV-2 RBD has a more compact conformation compared to the SARS-CoV RBD, with several residue changes stabilizing two virus-binding hotspots at the RBD–ACE2 interface, increasing the affinity for ACE2 binding. Additionally, they show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses human ACE2 as its receptor, suggesting a potential animal-to-human transmission route. The study provides insights into the molecular mechanisms of receptor recognition by SARS-CoV-2 and can guide intervention strategies targeting this process.The study investigates the structural basis of receptor recognition by SARS-CoV-2, a novel coronavirus that has emerged and rapidly spread, causing the COVID-19 pandemic. The virus recognizes angiotensin-converting enzyme 2 (ACE2) as its receptor, similar to SARS-CoV. The researchers determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein complexed with ACE2. They found that the SARS-CoV-2 RBD has a more compact conformation compared to the SARS-CoV RBD, with several residue changes stabilizing two virus-binding hotspots at the RBD–ACE2 interface, increasing the affinity for ACE2 binding. Additionally, they show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses human ACE2 as its receptor, suggesting a potential animal-to-human transmission route. The study provides insights into the molecular mechanisms of receptor recognition by SARS-CoV-2 and can guide intervention strategies targeting this process.