Impact of mutations in SARS-CoV-2 recombinant sub-variant XBB.1.16 on the binding affinity with human ACE2 receptor.

ABSTRACT

Despite the waning threat of the COVID-19 pandemic, its detrimental impact on global health persists. Regardless of natural immunity or immunity obtained through vaccination, emerging variants of the virus continue to undergo mutations and propagate globally. The persistent mutations in SARS-CoV-2, along with the subsequent formation of recombinant sub-variants has become a challenge for researchers and health professionals, raising concerns about the efficacy of current vaccines. Gaining a better understanding of the biochemical interactions between the Spike Protein (RBD) of SARS-CoV-2 variants and the human ACE2 receptor can prove to be beneficial in designing and developing antiviral therapeutics that are equally effective against all strains and emerging variants. Our objective in this study was to investigate the interfacial binding pattern of the SARS-CoV-2 RBD-ACE2 complex of the Wild Type (WT), Omicron, and the Omicron recombinant sub-variant XBB.1.16. We aimed to examine the atomic level factors and observe how mutations influence the interaction between the virus and its host using Molecular Dynamics simulation, MM/GBSA energy calculations, and Principal Component Analysis. Our findings reveal a higher degree of structural deviation and flexibility in XBB.1.16 compared to WT and Omicron. PCA indicated a wider cluster and significant flexibility in the movements of XBB.1.16 which can also be observed in free energy landscapes, while the normal mode analysis revealed converging motions within the RBD-ACE2 complexes which can facilitate the interaction between them. A pattern of decreased binding affinity was observed in case of XBB.1.16 when compared to the WT and Omicron. These observed deviations in XBB.1.16 when compared to its parent lineage Omicron, and WT can be attributed to the mutations specific to it. Collectively, these results enhance our understanding of the impact of mutations on the interaction between this strain and the host, taking us one step closer to designing effective antiviral therapeutics against the continually mutating strains.