Computational assessment of spike-hACE2 binding affinity in omicron subvariant BA.2.86

Abstract

The COVID-19 pandemic is ongoing and spreading around the world which Omicron and its subvariants lead to. Omicron constantly accumulates numerous Spike (S) protein mutations, increasing binding affinity with hACE2. A novel Omicron subvariant, BA.2.86, was rapidly classified into VUM (Variants Under Monitor) which had more amino acid mutation in S protein than prior Omicron subvariants. This work aimed to validate the mutation’s effective BA.2.86 S protein binding with hACE2. The analyzed in silico binding dynamics between BA.2.86 displayed for this variant behaved similarly to the Omicron BA.2 variant. The deletion V483 located in the Receptor Binding Motif (RBM) reduced the flexibility of residues in the interface that directly interacted with hACE2. Comparing BA.2.86 with BA.2, we found new mutations in the RBD including G339H, K356T, V445H, G446S, N450D, L452W, V483 deletion and F486P, resulting in a decreased binding free energy (BFE) with ACE2. Conversely, mutations R403K, N460K and N481K in BA.2.86 have increased the BFE. BA.2.86 not only stored new mutation decreased binding affinity, but specifically reduced the BFE of Q498R mutation. Overall, this study provided a basis for the low binding affinity of the new BA.2.86 when compared with prior Omicron and its subvariants.