RAISE: A computational tool for evaluating sarbecovirus spillover potential.
He Huang1,2,3
Lupeng Kong4
Yanzhi Zhu1,4
Yue Dai1,4
Yutong Yang1,4
Yuyang Wang1,2
Zhiqiang Wu1,2
Yi Qin Gao5,6
Lili Ren7,8,9
Affiliations9 institutions
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, Christophe Mérieux Laboratory, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Beijing, PR China.
Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, PR China.
Changping Laboratory, Beijing, PR China.
New Cornerstone Science Laboratory, College of Chemistry and Molecular Engineering, Peking University, Beijing, PR China. [email protected].
Beijing National Laboratory for Molecular Sciences, Beijing, PR China. [email protected].
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, Christophe Mérieux Laboratory, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China. [email protected].
Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Beijing, PR China. [email protected].
Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, Beijing, PR China. [email protected].
Animal sarbecoviruses, relatives of SARS-CoV or SARS-CoV-2, pose a significant zoonotic threat driven by their ability to bind the human ACE2 (hACE2) receptor. To address challenges in evaluating these threats, we developed RAISE (Receptor binding domain-hACE2 Interaction Scoring Evaluation), a computational framework that integrates structural predictions with interaction scoring. By scoring predicted hACE2 interactions, our RAISE model categorized sarbecoviruses into three groups: high potential (hACE2-binding), negligible potential (hACE2-nonbinding), and an intermediate "poised" state (a state defined by either weak binding activity or a high potential to evolve it). Mutation screening of two "hACE2-poised" sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species. The model's generalizability was further demonstrated through prospective application to merbecoviruses, highlighting its utility in preemptively assessing zoonotic threats across coronavirus lineages. RAISE provides a predictive roadmap for prioritizing risk viruses and guiding pandemic preparedness.
Structured evidence records
Evidence records
6 total
Genomic Evolution2 records
Genomic EvolutionExtraction confidence 0.75
Key finding
Mutation analysis of sarbecoviruses PDF-2370 and Khosta-1 identified amino acid changes T498Y/W that enabled human ACE2 binding and expanded host species potential.
Mutation screening of two "hACE2-poised" sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
Genes or proteins
Receptor binding domain
Analysis methods
mutation screening; computational model
Genomic EvolutionExtraction confidence 0.75
Key finding
Mutation analysis of sarbecovirus Khosta-1 showed that changes such as T498Y/W allowed human ACE2 receptor utilization and expansion of host range.
Mutation screening of two "hACE2-poised" sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
Genes or proteins
Receptor binding domain
Analysis methods
mutation screening; computational model
Molecular Adaptation2 records
Molecular AdaptationExtraction confidence 0.95
Key finding
The T498Y/W mutations in PDF-2370 and Khosta-1 enabled these sarbecoviruses to utilize human ACE2 and expanded their receptor-binding range across species.
Mutation screening of two 'hACE2-poised' sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
Mutation screening of two 'hACE2-poised' sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
Animal sarbecoviruses, relatives of SARS-CoV or SARS-CoV-2, pose a significant zoonotic threat driven by their ability to bind the human ACE2 (hACE2) receptor. Mutation screening of two 'hACE2-poised' sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
Mutation screening of two 'hACE2-poised' sarbecoviruses, PDF-2370 and Khosta-1 using RAISE, revealed mutations such as T498Y/W that enabled human ACE2 utilization and expanded their ability to bind to ACE2 receptors from a broader range of species.
