Mechanism Behind the Higher Affinity of ACE2 to SARS-CoV-2 Compared with SARS-CoV-1
- The COVID-19 virus led a devastating impact around the world.
- The COVID-19 virus uses the receptor-binding domain (RBD) of its spike protein to interact with the angiotensin-converting enzyme 2 (ACE2) of human cells.
- The COVID-19 virus enters a host cell following the interaction of RBD and ACE2.
- Studies have shown that ACE2 interacts with the COVID-19 viral spike protein with higher affinity compared to the spike protein of SARS virus or SARS-CoV-1.
- The mechanism behind the affinity difference is not well understood.
- Researchers quantified the interaction between COVID-19 viral RBD and ACE2 as well as the interaction between SARS-CoV-1 RBD and ACE2.
- The unbinding forces between COVID-19 viral RBD and ACE2 are about 35% higher compared to those of SARS-CoV-1 RBD and ACE2.
- Data suggest that the COVID-19 viral RBD interacts with the N-linked glycan on Asn90 of ACE2.
- RBD interaction with the N-linked glycan was not observed in the SARS-CoV-1 RBD-ACE2 complex.
- The RBD-N-glycan interaction adds force and prolongs the interaction time between the virus and host cell.
- Researchers removed the N-linked glycans on ACE2 and found that the binding strength of COVID-19 RBD have decreased.
- The results revealed the mechanism behind the difference in ACE2 binding affinity between COVID-19 virus and SARS-CoV-1.
Cao, W., et. Al. (2021). Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction. Biophysical Journal VOLUME 120, ISSUE 6, P1011-1019. https://doi.org/10.1016/j.bpj.2021.02.007