The B.1.1.7 variant of the SARS-CoV-2 virus shows enhanced infectiousness over the wild type virus, leading to increasing patient numbers in affected areas. Amino acid exchanges within the SARS-CoV-2 spike protein variant of B.1.1.7 affect inter-monomeric contact sites within the trimer (A570D and D614G) as well as the ACE2-receptor interface region (N501Y), which comprises the receptor-binding domain (RBD) of the spike protein. However, the molecular consequences of mutations within B.1.1.7 on spike protein dynamics and stability or ACE2 binding are largely unknown. Here, molecular dynamics simulations comparing SARS-CoV-2 wild type with the B.1.1.7 variant revealed inter-trimeric contact rearrangements, altering the structural flexibility within the spike protein trimer. Furthermore, we found increased flexibility in direct spatial proximity of the fusion peptide due to salt bridge rearrangements induced by the D614G mutation in B.1.1.7. This study also implies a reduced binding affinity for B.1.1.7 with ACE2, as the N501Y mutation restructures the RBD–ACE2 interface, significantly decreasing the linear interaction energy between the RBD and ACE2. Our results demonstrate how mutations found within B.1.1.7 enlarge the flexibility around the fusion peptide and change the RBD–ACE2 interface. We anticipate our findings to be starting points for in depth biochemical and cell biological analyses of B.1.1.7.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, Molecular dynamics simulation, B.1.1.7, Receptor binding, 【초록키워드】 Mutation, variant, virus, binding affinity, Spike protein, B.1.1.7 variant, stability, D614G mutation, RBD, N501Y, Patient, D614G, N501Y mutation, molecular, fusion peptide, wild type, Interaction, Analysis, ACE2 binding, Contact, starting point, biochemical, trimer, A570D, Affect, Cell, consequence, Salt Bridge, interface region, affected, significantly, linear, reduced, the spike protein, the RBD, the receptor-binding domain, structural flexibility, The B.1.1.7, the SARS-CoV-2, the SARS-CoV-2 virus, 【제목키워드】 spike, fusion, affinity,