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Commun Biol
. 2025 Aug 30;8(1):1322.
doi: 10.1038/s42003-025-08768-4. Engineering virus-like particles for safe and versatile modeling of SARS-CoV-2 host interaction and immune escape
Liang Ma # 1 2 , Yuan Lin # 3 , Siyu Ma 1 2 4 , Kai Chen 1 2 , Yihan Lin 5 6 7
Affiliations
The continuous evolution of SARS-CoV-2 poses global health challenges. A safe, rapid, and versatile method for assessing functions of Spike protein mutations in ACE2 receptor binding and immune evasion would be highly valuable. To address this, we engineered a transcription- and replication-competent virus-like particle (trVLP) derived from the Sindbis virus, pseudotyped with the SARS-CoV-2 receptor binding domain (RBD). This trVLP exclusively propagates in BHK-21 cells engineered to express both RNA replicase and human ACE2, providing a controllable, safe model of SARS-CoV-2 RBD-ACE2 interaction-mediated virus entry. The system enables characterization of RBD interactions with ACE2 from various mammalian hosts, demonstrating its utility for studying host-virus interactions. By leveraging the evolutionary capability of trVLP mediated by error-prone RNA replication, we screened for RBD variants that evade the antibody-mediated inhibition of cell entry. Together, these findings underscore the utility of the trVLP as a safe, rapid, and flexible platform for dissecting SARS-CoV-2 RBD evolution and identifying key adaptive mutations with implications for surveillance and countermeasure development.
. 2025 Aug 30;8(1):1322.
doi: 10.1038/s42003-025-08768-4. Engineering virus-like particles for safe and versatile modeling of SARS-CoV-2 host interaction and immune escape
Liang Ma # 1 2 , Yuan Lin # 3 , Siyu Ma 1 2 4 , Kai Chen 1 2 , Yihan Lin 5 6 7
Affiliations
- PMID: 40885856
- PMCID: PMC12398559
- DOI: 10.1038/s42003-025-08768-4
The continuous evolution of SARS-CoV-2 poses global health challenges. A safe, rapid, and versatile method for assessing functions of Spike protein mutations in ACE2 receptor binding and immune evasion would be highly valuable. To address this, we engineered a transcription- and replication-competent virus-like particle (trVLP) derived from the Sindbis virus, pseudotyped with the SARS-CoV-2 receptor binding domain (RBD). This trVLP exclusively propagates in BHK-21 cells engineered to express both RNA replicase and human ACE2, providing a controllable, safe model of SARS-CoV-2 RBD-ACE2 interaction-mediated virus entry. The system enables characterization of RBD interactions with ACE2 from various mammalian hosts, demonstrating its utility for studying host-virus interactions. By leveraging the evolutionary capability of trVLP mediated by error-prone RNA replication, we screened for RBD variants that evade the antibody-mediated inhibition of cell entry. Together, these findings underscore the utility of the trVLP as a safe, rapid, and flexible platform for dissecting SARS-CoV-2 RBD evolution and identifying key adaptive mutations with implications for surveillance and countermeasure development.